1. Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China 2. Research and Development Center of Chinese Medicine Resources and Biotechnology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as “top to bottom.” However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone’s physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the “bottom-up” progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.
2017 Disease GBD, Incidence Injury, Collaborators Prevalence. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392(10159): 1789–1858 https://doi.org/10.1016/S0140-6736(18)32279-7
2
JG Quicke, PG Conaghan, N Corp, G Peat. Osteoarthritis year in review 2021: epidemiology & therapy. Osteoarthritis Cartilage 2022; 30(2): 196–206 https://doi.org/10.1016/j.joca.2021.10.003
3
MHM Yunus, A Nordin, H Kamal. Pathophysiological perspective of osteoarthritis. Medicina (Kaunas) 2020; 56(11): 614–627 https://doi.org/10.3390/medicina56110614
4
RF Loeser, SR Goldring, CR Scanzello, MB Goldring. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012; 64(6): 1697–1707 https://doi.org/10.1002/art.34453
5
N Aizah, PP Chong, T Kamarul. Early alterations of subchondral bone in the rat anterior cruciate ligament transection model of osteoarthritis. Cartilage 2021; 13(2_suppl): 1322S–1333S https://doi.org/10.1177/1947603519878479
6
X Zhu, YT Chan, PSH Yung, RS Tuan, Y Jiang. Subchondral bone remodeling: a therapeutic target for osteoarthritis. Front Cell Dev Biol 2021; 8: 607764 https://doi.org/10.3389/fcell.2020.607764
JP Mansell, C Collins, AJ Bailey. Bone, not cartilage, should be the major focus in osteoarthritis. Nat Clin Pract Rheumatol 2007; 3(6): 306–307 https://doi.org/10.1038/ncprheum0505
9
Y Henrotin, L Pesesse, C Sanchez. Subchondral bone and osteoarthritis: biological and cellular aspects. Osteoporos Int 2012; 23(Suppl 8): S847–S851 https://doi.org/10.1007/s00198-012-2162-z
10
W Hu, Y Chen, C Dou, S Dong. Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis. Ann Rheum Dis 2021; 80(4): 413–422 https://doi.org/10.1136/annrheumdis-2020-218089
11
PR Coryell, BO Diekman, RF Loeser. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis. Nat Rev Rheumatol 2021; 17(1): 47–57 https://doi.org/10.1038/s41584-020-00533-7
12
M Darbandi, FK Shadmani, M Miryan, M Ghalandari, M Mohebi, SA Jam, Y Pasdar. The burden of osteoarthritis due to high body mass index in Iran from 1990 to 2019. Sci Rep 2023; 13(1): 11710–11719 https://doi.org/10.1038/s41598-023-37780-z
13
E Poulsen, GH Goncalves, A Bricca, EM Roos, JB Thorlund, CB Juhl. Knee osteoarthritis risk is increased 4–6 fold after knee injury—a systematic review and meta-analysis. Br J Sports Med 2019; 53(23): 1454–1463 https://doi.org/10.1136/bjsports-2018-100022
14
R Papalia, G Torre, B Zampogna, F Vorini, A Grasso, V Denaro. Sport activity as risk factor for early knee osteoarthritis. J Biol Regul Homeost Agents 2019; 33(2 Suppl. 1): 29–37, XIX
15
X Liang, OHI Chou, CL Cheung, BMY Cheung. Is hypertension associated with arthritis? The United States national health and nutrition examination survey 1999–2018.. Ann Med 2022; 54(1): 1767–1775 https://doi.org/10.1080/07853890.2022.2089911
16
M Peshkova, A Lychagin, M Lipina, B Di Matteo, G Anzillotti, F Ronzoni, N Kosheleva, A Shpichka, V Royuk, V Fomin, E Kalinsky, P Timashev, E Kon. Gender-related aspects in osteoarthritis development and progression: a review. Int J Mol Sci 2022; 23(5): 2767–2788 https://doi.org/10.3390/ijms23052767
17
CG Boer, K Hatzikotoulas, L Southam, L Stefánsdóttir, Y Zhang, de Almeida R Coutinho, TT Wu, J Zheng, A Hartley, M Teder-Laving, AH Skogholt, C Terao, E Zengini, G Alexiadis, A Barysenka, G Bjornsdottir, ME Gabrielsen, A Gilly, T Ingvarsson, MB Johnsen, H Jonsson, M Kloppenburg, A Luetge, SH Lund, R Mägi, M Mangino, RRGHH Nelissen, M Shivakumar, J Steinberg, H Takuwa, LF Thomas, M; arcOGEN Consortium; HUNT All-In Pain; ARGO Consortium; Regeneron Genetics Center; Babis GC Tuerlings, JPY Cheung, JH Kang, P Kraft, SA Lietman, D Samartzis, PE Slagboom, K Stefansson, U Thorsteinsdottir, JH Tobias, AG Uitterlinden, B Winsvold, JA Zwart, Smith G Davey, PC Sham, G Thorleifsson, TR Gaunt, AP Morris, AM Valdes, A Tsezou, KSE Cheah, S Ikegawa, K Hveem, T Esko, JM Wilkinson, I Meulenbelt, MTM Lee, Meurs JBJ van, U Styrkársdóttir, E Zeggini. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell 2021; 184(18): 4784–4818.e17 https://doi.org/10.1016/j.cell.2021.07.038
18
Q Yao, X Wu, C Tao, W Gong, M Chen, M Qu, Y Zhong, T He, S Chen, G Xiao. Osteoarthritis: pathogenic signaling pathways and therapeutic targets. Signal Transduct Target Ther 2023; 8(1): 56–87 https://doi.org/10.1038/s41392-023-01330-w
S Safiri, AA Kolahi, E Smith, C Hill, D Bettampadi, MA Mansournia, D Hoy, A Ashrafi-Asgarabad, M Sepidarkish, A Almasi-Hashiani, G Collins, J Kaufman, M Qorbani, M Moradi-Lakeh, AD Woolf, F Guillemin, L March, M Cross. Global, regional and national burden of osteoarthritis 1990–2017: a systematic analysis of the Global Burden of Disease Study 2017. Ann Rheum Dis 2020; 79(6): 819–828 https://doi.org/10.1136/annrheumdis-2019-216515
21
H Long, Q Liu, H Yin, K Wang, N Diao, Y Zhang, J Lin, A Guo. Prevalence trends of site-specific osteoarthritis from 1990 to 2019: findings from the global burden of disease study 2019. Arthritis Rheumatol 2022; 74(7): 1172–1183 https://doi.org/10.1002/art.42089
22
Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basáez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabé E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, Fèvre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gosselin R, Grainger R, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Ma J, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Mensah GA, Merriman TR, Meyer AC, Miglioli V, Miller M, Miller TR, Mitchell PB, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KM, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O’Donnell M, O’Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA 3rd, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, De Leòn FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJ, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC, Williams SR, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AK, Zheng ZJ, Zonies D, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2163–2196 doi:10.1016/S0140-6736(12)61729-2 PMID:23245607
23
D Li, S Li, Q Chen, X Xie. The prevalence of symptomatic knee osteoarthritis in relation to age, sex, area, region, and body mass index in China: a systematic review and meta-analysis. Front Med (Lausanne) 2020; 7: 304–316 https://doi.org/10.3389/fmed.2020.00304
24
JW Hong, JH Noh, DJ Kim. The prevalence of and demographic factors associated with radiographic knee osteoarthritis in Korean adults aged ≥ 50 years: the 2010–2013 Korea National Health and Nutrition Examination Survey. PLoS One 2020; 15(3): e0230613 https://doi.org/10.1371/journal.pone.0230613
25
Y Li, W Xie, W Xiao, D Dou. Progress in osteoarthritis research by the national natural science foundation of China. Bone Res 2022; 10(1): 41–53 https://doi.org/10.1038/s41413-022-00207-y
26
C Kim, KD Linsenmeyer, SC Vlad, A Guermazi, MM Clancy, J Niu, DT Felson. Prevalence of radiographic and symptomatic hip osteoarthritis in an urban United States community: the Framingham osteoarthritis study. Arthritis Rheumatol 2014; 66(11): 3013–3017 https://doi.org/10.1002/art.38795
27
Z Fan, L Yan, H Liu, X Li, K Fan, Q Liu, JJ Li, B Wang. The prevalence of hip osteoarthritis: a systematic review and meta-analysis. Arthritis Res Ther 2023; 25(1): 51–62 https://doi.org/10.1186/s13075-023-03033-7
28
2016 Causes of Death Collaborators GBD. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100): 1151–1210 https://doi.org/10.1016/S0140-6736(17)32152-9
29
2019 Diseases GBD, Collaborators Injuries. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020; 396(10258): 1204–1222 https://doi.org/10.1016/S0140-6736(20)30925-9
30
X Tang, S Wang, S Zhan, J Niu, K Tao, Y Zhang, J Lin. The prevalence of symptomatic knee osteoarthritis in China: results from the China health and retirement longitudinal study. Arthritis Rheumatol 2016; 68(3): 648–653 https://doi.org/10.1002/art.39465
31
JB Driban, MS Harkey, MF Barbe, RJ Ward, JW MacKay, JE Davis, B Lu, LL Price, CB Eaton, GH Lo, TE McAlindon. Risk factors and the natural history of accelerated knee osteoarthritis: a narrative review. BMC Musculoskelet Disord 2020; 21(1): 332–343 https://doi.org/10.1186/s12891-020-03367-2
32
J Lo, L Chan, S Flynn. A systematic review of the incidence, prevalence, costs, and activity and work limitations of amputation, osteoarthritis, rheumatoid arthritis, back pain, multiple sclerosis, spinal cord injury, stroke, and traumatic brain injury in the United States: a 2019 update. Arch Phys Med Rehabil 2021; 102(1): 115–131 https://doi.org/10.1016/j.apmr.2020.04.001
33
SX Wang, AX Ganguli, A Bodhani, JK Medema, WM Reichmann, D Macaulay. Healthcare resource utilization and costs by age and joint location among osteoarthritis patients in a privately insured population. J Med Econ 2017; 20(12): 1299–1306 https://doi.org/10.1080/13696998.2017.1377717
34
DJ Hunter, M Nevitt, E Losina, V Kraus. Biomarkers for osteoarthritis: current position and steps towards further validation. Best Pract Res Clin Rheumatol 2014; 28(1): 61–71 https://doi.org/10.1016/j.berh.2014.01.007
35
X Zhou, H Cao, Y Yuan, W Wu. Biochemical signals mediate the crosstalk between cartilage and bone in osteoarthritis. BioMed Res Int 2020; 2020: 5720360 https://doi.org/10.1155/2020/5720360
P Lu, K Takai, VM Weaver, Z Werb. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol 2011; 3(12): a005058 https://doi.org/10.1101/cshperspect.a005058
38
S Chen, P Fu, H Wu, M Pei. Meniscus, articular cartilage and nucleus pulposus: a comparative review of cartilage-like tissues in anatomy, development and function. Cell Tissue Res 2017; 370(1): 53–70 https://doi.org/10.1007/s00441-017-2613-0
GW Greene, X Banquy, DW Lee, DD Lowrey, J Yu, JN Israelachvili. Adaptive mechanically controlled lubrication mechanism found in articular joints. Proc Natl Acad Sci USA 2011; 108(13): 5255–5259 https://doi.org/10.1073/pnas.1101002108
41
AA Mieloch, M Richter, T Trzeciak, M Giersig, JD Rybka. Osteoarthritis severely decreases the elasticity and hardness of knee joint cartilage: a nanoindentation study. J Clin Med 2019; 8(11): 1865–1876 https://doi.org/10.3390/jcm8111865
42
CD Hoemann, CH Lafantaisie-Favreau, V Lascau-Coman, G Chen, J Guzmán-Morales. The cartilage-bone interface. J Knee Surg 2012; 25(2): 85–97 https://doi.org/10.1055/s-0032-1319782
43
J Yu, F Liang, H Huang, P Pirttiniemi, D Yu. Effects of loading on chondrocyte hypoxia, HIF-1α and VEGF in the mandibular condylar cartilage of young rats. Orthod Craniofac Res 2018; 21(1): 41–47 https://doi.org/10.1111/ocr.12212
44
J Pan, X Zhou, W Li, JE Novotny, SB Doty, L Wang. In situ measurement of transport between subchondral bone and articular cartilage. J Orthop Res 2009; 27(10): 1347–1352 https://doi.org/10.1002/jor.20883
45
SR Goldring, MB Goldring. Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk. Nat Rev Rheumatol 2016; 12(11): 632–644 https://doi.org/10.1038/nrrheum.2016.148
46
MB Goldring, SR Goldring. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci 2010; 1192(1): 230–237 https://doi.org/10.1111/j.1749-6632.2009.05240.x
47
SJO Rytky, L Huang, P Tanska, A Tiulpin, E Panfilov, W Herzog, RK Korhonen, S Saarakkala, MAJ Finnilä. Automated analysis of rabbit knee calcified cartilage morphology using micro-computed tomography and deep learning. J Anat 2021; 239(2): 251–263 https://doi.org/10.1111/joa.13435
48
H Madry, CN van Dijk, M Mueller-Gerbl. The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc 2010; 18(4): 419–433 https://doi.org/10.1007/s00167-010-1054-z
49
JM Berthelot, J Sellam, Y Maugars, F Berenbaum. Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis. RMD Open 2019; 5(2): e001037 https://doi.org/10.1136/rmdopen-2019-001037
50
S Milz, R Putz. Quantitative morphology of the subchondral plate of the tibial plateau. J Anat 1994; 185(Pt 1): 103–110
X Zhu, YT Chan, PSH Yung, RS Tuan, Y Jiang. Subchondral bone remodeling: a therapeutic target for osteoarthritis. Front Cell Dev Biol 2021; 8: 607764 https://doi.org/10.3389/fcell.2020.607764
53
S Taheri, T Winkler, LS Schenk, C Neuerburg, SF Baumbach, J Zustin, W Lehmann, AF Schilling. Developmental transformation and reduction of connective cavities within the subchondral bone. Int J Mol Sci 2019; 20(3): 770–783 https://doi.org/10.3390/ijms20030770
54
JT Holopainen, PA Brama, E Halmesmäki, T Harjula, J Tuukkanen, Weeren PR van, HJ Helminen, MM Hyttinen. Changes in subchondral bone mineral density and collagen matrix organization in growing horses. Bone 2008; 43(6): 1108–1114 https://doi.org/10.1016/j.bone.2008.07.254
55
JS Day, JC Van Der Linden, RA Bank, M Ding, I Hvid, DR Sumner, H Weinans. Adaptation of subchondral bone in osteoarthritis. Biorheology 2004; 41(3–4): 359–368
G Zhen, C Wen, X Jia, Y Li, JL Crane, SC Mears, FB Askin, FJ Frassica, W Chang, J Yao, JA Carrino, A Cosgarea, D Artemov, Q Chen, Z Zhao, X Zhou, L Riley, P Sponseller, M Wan, WW Lu, X Cao. Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med 2013; 19(6): 704–712 https://doi.org/10.1038/nm.3143
58
NLA Fell, BM Lawless, SC Cox, ME Cooke, NM Eisenstein, DET Shepherd, DM Espino. The role of subchondral bone, and its histomorphology, on the dynamic viscoelasticity of cartilage, bone and osteochondral cores. Osteoarthritis Cartilage 2019; 27(3): 535–543 https://doi.org/10.1016/j.joca.2018.12.006
59
EL Radin, RB Martin, DB Burr, B Caterson, RD Boyd, C Goodwin. Effects of mechanical loading on the tissues of the rabbit knee. J Orthop Res 1984; 2(3): 221–234 https://doi.org/10.1002/jor.1100020303
XS Liu, P Sajda, PK Saha, FW Wehrli, G Bevill, TM Keaveny, XE Guo. Complete volumetric decomposition of individual trabecular plates and rods and its morphological correlations with anisotropic elastic moduli in human trabecular bone. J Bone Miner Res 2008; 23(2): 223–235 https://doi.org/10.1359/jbmr.071009
62
J Wang, B Zhou, XS Liu, AJ Fields, A Sanyal, X Shi, M Adams, TM Keaveny, XE Guo. Trabecular plates and rods determine elastic modulus and yield strength of human trabecular bone. Bone 2015; 72: 71–80 https://doi.org/10.1016/j.bone.2014.11.006
63
MS O’Brien, JJ McDougall. Age and frailty as risk factors for the development of osteoarthritis. Mech Ageing Dev 2019; 180: 21–28 https://doi.org/10.1016/j.mad.2019.03.003
64
R Ding, N Zhang, Q Wang, W Wang. Alterations of the subchondral bone in osteoarthritis: complying with Wolff’s law. Curr Rheumatol Rev 2022; 18(3): 178–185 https://doi.org/10.2174/1573397118666220401104428
65
AJ Teichtahl, AE Wluka, P Wijethilake, Y Wang, A Ghasem-Zadeh, FM Cicuttini. Wolff’s law in action: a mechanism for early knee osteoarthritis. Arthritis Res Ther 2015; 17(1): 207–216 https://doi.org/10.1186/s13075-015-0738-7
66
J Zhang, S Chen, W Chen, Y Huang, R Lin, M Huang, Y Wu, L Zheng, Z Li, N Liao, J Ye, X Liu. Ultrastructural change of the subchondral bone increases the severity of cartilage damage in osteoporotic osteoarthritis of the knee in rabbits. Pathol Res Pract 2018; 214(1): 38–43 https://doi.org/10.1016/j.prp.2017.11.018
67
Y Chen, Y Hu, YE Yu, X Zhang, T Watts, B Zhou, J Wang, T Wang, W Zhao, KY Chiu, FK Leung, X Cao, W Macaulay, KK Nishiyama, E Shane, WW Lu, XE Guo. Subchondral trabecular rod loss and plate thickening in the development of osteoarthritis. J Bone Miner Res 2018; 33(2): 316–327 https://doi.org/10.1002/jbmr.3313
68
Z Zamli, K Robson Brown, M Sharif. Subchondral bone plate changes more rapidly than trabecular bone in osteoarthritis. Int J Mol Sci 2016; 17(9): 1496–1507 https://doi.org/10.3390/ijms17091496
69
F Intema, HA Hazewinkel, D Gouwens, JW Bijlsma, H Weinans, FP Lafeber, SC Mastbergen. In early OA, thinning of the subchondral plate is directly related to cartilage damage: results from a canine ACLT-meniscectomy model. Osteoarthritis Cartilage 2010; 18(5): 691–698 https://doi.org/10.1016/j.joca.2010.01.004
70
SM Botter, GJ van Osch, S Clockaerts, JH Waarsing, H Weinans, JP van Leeuwen. Osteoarthritis induction leads to early and temporal subchondral plate porosity in the tibial plateau of mice: an in vivo microfocal computed tomography study. Arthritis Rheum 2011; 63(9): 2690–2699 https://doi.org/10.1002/art.30307
P Pu, M Qingyuan, W Weishan, H Fei, M Tengyang, Z Weiping, Z Zhoujun, W Mengyu, W Chao, S Chong. Protein-degrading enzymes in osteoarthritis. Z Orthop Unfall 2021; 159(1): 54–66 https://doi.org/10.1055/a-1019-8117
73
SY Tang, RP Herber, SP Ho, T Alliston. Matrix metalloproteinase-13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance. J Bone Miner Res 2012; 27(9): 1936–1950 https://doi.org/10.1002/jbmr.1646
G Borciani, G Montalbano, N Baldini, G Cerqueni, C Vitale-Brovarone, G Ciapetti. Co-culture systems of osteoblasts and osteoclasts: simulating in vitro bone remodeling in regenerative approaches. Acta Biomater 2020; 108: 22–45 https://doi.org/10.1016/j.actbio.2020.03.043
W Su, G Liu, X Liu, Y Zhou, Q Sun, G Zhen, X Wang, Y Hu, P Gao, S Demehri, X Cao, M Wan. Angiogenesis stimulated by elevated PDGF-BB in subchondral bone contributes to osteoarthritis development. JCI Insight 2020; 5(8): e135446 https://doi.org/10.1172/jci.insight.135446
78
S Zhu, J Zhu, G Zhen, Y Hu, S An, Y Li, Q Zheng, Z Chen, Y Yang, M Wan, RL Skolasky, Y Cao, T Wu, B Gao, M Yang, M Gao, J Kuliwaba, S Ni, L Wang, C Wu, D Findlay, HK Eltzschig, HW Ouyang, J Crane, FQ Zhou, Y Guan, X Dong, X Cao. Subchondral bone osteoclasts induce sensory innervation and osteoarthritis pain. J Clin Invest 2019; 129(3): 1076–1093 https://doi.org/10.1172/JCI121561
79
W Jiang, Y Jin, S Zhang, Y Ding, K Huo, J Yang, L Zhao, B Nian, TP Zhong, W Lu, H Zhang, X Cao, KM Shah, N Wang, M Liu, J Luo. PGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoarthritis. Bone Res 2022; 10(1): 27–43 https://doi.org/10.1038/s41413-022-00201-4
80
P Ren, H Niu, H Cen, S Jia, H Gong, Y Fan. Biochemical and morphological abnormalities of subchondral bone and their association with cartilage degeneration in spontaneous osteoarthritis. Calcif Tissue Int 2021; 109(2): 179–189 https://doi.org/10.1007/s00223-021-00834-3
81
M Haneda, MF Rai, L Cai, RH Brophy, RJ O’Keefe, JC Clohisy, C Pascual-Garrido. Distinct pattern of inflammation of articular cartilage and the synovium in early and late hip femoroacetabular impingement. Am J Sports Med 2020; 48(10): 2481–2488 https://doi.org/10.1177/0363546520935440
82
GJ Kazakia, D Kuo, J Schooler, S Siddiqui, S Shanbhag, G Bernstein, A Horvai, S Majumdar, M Ries, X Li. Bone and cartilage demonstrate changes localized to bone marrow edema-like lesions within osteoarthritic knees. Osteoarthritis Cartilage 2013; 21(1): 94–101 https://doi.org/10.1016/j.joca.2012.09.008
H Leydet-Quilici, T Le Corroller, C Bouvier, R Giorgi, JN Argenson, P Champsaur, T Pham, AM de Paula, P Lafforgue. Advanced hip osteoarthritis: magnetic resonance imaging aspects and histopathology correlations. Osteoarthritis Cartilage 2010; 18(11): 1429–1435 https://doi.org/10.1016/j.joca.2010.08.008
85
E Kon, M Ronga, G Filardo, J Farr, H Madry, G Milano, L Andriolo, N Shabshin. Bone marrow lesions and subchondral bone pathology of the knee. Knee Surg Sports Traumatol Arthrosc 2016; 24(6): 1797–1814 https://doi.org/10.1007/s00167-016-4113-2
86
D Muratovic, DM Findlay, FM Cicuttini, AE Wluka, YR Lee, S Edwards, JS Kuliwaba. Bone marrow lesions in knee osteoarthritis: regional differences in tibial subchondral bone microstructure and their association with cartilage degeneration. Osteoarthritis Cartilage 2019; 27(11): 1653–1662 https://doi.org/10.1016/j.joca.2019.07.004
87
S Koushesh, SM Shahtaheri, DF McWilliams, DA Walsh, MN Sheppard, J Westaby, SM Haybatollahi, FA Howe, N Sofat. The osteoarthritis bone score (OABS): a new histological scoring system for the characterisation of bone marrow lesions in osteoarthritis. Osteoarthritis Cartilage 2022; 30(5): 746–755 https://doi.org/10.1016/j.joca.2022.01.008
88
A Kuttapitiya, L Assi, K Laing, C Hing, P Mitchell, G Whitley, A Harrison, FA Howe, V Ejindu, C Heron, N Sofat. Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation. Ann Rheum Dis 2017; 76(10): 1764–1773 https://doi.org/10.1136/annrheumdis-2017-211396
89
LN Nwosu, M Allen, L Wyatt, JL Huebner, V Chapman, DA Walsh, VB Kraus. Pain prediction by serum biomarkers of bone turnover in people with knee osteoarthritis: an observational study of TRAcP5b and cathepsin K in OA. Osteoarthritis Cartilage 2017; 25(6): 858–865 https://doi.org/10.1016/j.joca.2017.01.002
90
M Zarka, E Hay, A Ostertag, C Marty, C Chappard, F Oudet, K Engelke, JD Laredo, M Cohen-Solal. Microcracks in subchondral bone plate is linked to less cartilage damage. Bone 2019; 123: 1–7 https://doi.org/10.1016/j.bone.2019.03.011
91
W Gilbert, R Bragg, AM Elmansi, ME McGee-Lawrence, CM Isales, MW Hamrick, WD Hill, S Fulzele. Stromal cell-derived factor-1 (CXCL12) and its role in bone and muscle biology. Cytokine 2019; 123: 154783 https://doi.org/10.1016/j.cyto.2019.154783
92
S Tonna, IJ Poulton, F Taykar, PW Ho, B Tonkin, B Crimeen-Irwin, L Tatarczuch, NE McGregor, EJ Mackie, TJ Martin, NA Sims. Chondrocytic ephrin B2 promotes cartilage destruction by osteoclasts in endochondral ossification. Development 2016; 143(4): 648–657
93
PI Croucher, MM McDonald, TJ Martin. Bone metastasis: the importance of the neighbourhood. Nat Rev Cancer 2016; 16(6): 373–386 https://doi.org/10.1038/nrc.2016.44
94
RK Zhang, GW Li, C Zeng, CX Lin, LS Huang, GX Huang, C Zhao, SY Feng, H Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018; 7(11): 587–594 https://doi.org/10.1302/2046-3758.711.BJR-2018-0057.R1
95
YK Jung, MS Han, HR Park, EJ Lee, JA Jang, GW Kim, SY Lee, D Moon, S Han. Calcium-phosphate complex increased during subchondral bone remodeling affects earlystage osteoarthritis. Sci Rep 2018; 8(1): 487–497 https://doi.org/10.1038/s41598-017-18946-y
96
MJ Pearson, D Herndler-Brandstetter, MA Tariq, TA Nicholson, AM Philp, HL Smith, ET Davis, SW Jones, JM Lord. IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity. Sci Rep 2017; 7(1): 3451–3462 https://doi.org/10.1038/s41598-017-03759-w
97
Y Cao, ID Jansen, S Sprangers, J Stap, PJ Leenen, V Everts, TJ de Vries. IL-1β differently stimulates proliferation and multinucleation of distinct mouse bone marrow osteoclast precursor subsets. J Leukoc Biol 2016; 100(3): 513–523 https://doi.org/10.1189/jlb.1A1215-543R
98
Q Tang, YW Su, CM Fan, R Chung, M Hassanshahi, Y Peymanfar, CJ Xian. Release of CXCL12 from apoptotic skeletal cells contributes to bone growth defects following dexamethasone therapy in rats. J Bone Miner Res 2020; 35(8): 1612–1613 https://doi.org/10.1002/jbmr.4034
99
L Chen, F Yao, T Wang, G Li, P Chen, M Bulsara, JJY Zheng, E Landao-Bassonga, M Firth, P Vasantharao, Y Huang, M Lorimer, S Graves, J Gao, R Carey-Smith, J Papadimitriou, C Zhang, D Wood, C Jones, M Zheng. Horizontal fissuring at the osteochondral interface: a novel and unique pathological feature in patients with obesity-related osteoarthritis. Ann Rheum Dis 2020; 79(6): 811–818 https://doi.org/10.1136/annrheumdis-2020-216942
100
XL Yuan, HY Meng, YC Wang, J Peng, QY Guo, AY Wang, SB Lu. Bone-cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies. Osteoarthritis Cartilage 2014; 22(8): 1077–1089 https://doi.org/10.1016/j.joca.2014.05.023
101
JA Carrino, J Blum, JA Parellada, ME Schweitzer, WB Morrison. MRI of bone marrow edema-like signal in the pathogenesis of subchondral cysts. Osteoarthritis Cartilage 2006; 14(10): 1081–1085 https://doi.org/10.1016/j.joca.2006.05.011
102
A Anwar, Z Hu, Y Zhang, Y Gao, C Tian, X Wang, MU Nazir, Y Wang, Z Zhao, D Lv, Z Zhang, H Zhang, G Lv. Multiple subchondral bone cysts cause deterioration of articular cartilage in medial OA of knee: a 3D simulation study. Front Bioeng Biotechnol 2020; 8: 573938 https://doi.org/10.3389/fbioe.2020.573938
103
TA Perry, TW O’Neill, I Tolstykh, J Lynch, DT Felson, NK Arden, MC Nevitt. Magnetic resonance imaging-assessed subchondral cysts and incident knee pain and knee osteoarthritis: data from the multicenter osteoarthritis study. Arthritis Rheumatol 2022; 74(1): 60–69 https://doi.org/10.1002/art.41917
104
A Nakasone, Y Guang, A Wise, L Kim, J Babbin, S Rathod, AJ Mitchell, LC Gerstenfeld, EF Morgan. Structural features of subchondral bone cysts and adjacent tissues in hip osteoarthritis. Osteoarthritis Cartilage 2022; 30(8): 1130–1139 https://doi.org/10.1016/j.joca.2022.03.013
105
B von Rechenberg, H Guenther, CW McIlwraith, C Leutenegger, DD Frisbie, MK Akens, JA Auer. Fibrous tissue of subchondral cystic lesions in horses produce local mediators and neutral metalloproteinases and cause bone resorption in vitro. Vet Surg 2000; 29(5): 420–429 https://doi.org/10.1053/jvet.2000.7538
106
HD Dürr, H Martin, C Pellengahr, M Schlemmer, M Maier, V Jansson. The cause of subchondral bone cysts in osteoarthrosis: a finite element analysis. Acta Orthop Scand 2004; 75(5): 554–558 https://doi.org/10.1080/00016470410001411
107
LG Cox, MW Lagemaat, CC van Donkelaar, B van Rietbergen, ML Reilingh, L Blankevoort, CN van Dijk, K Ito. The role of pressurized fluid in subchondral bone cyst growth. Bone 2011; 49(4): 762–768 https://doi.org/10.1016/j.bone.2011.06.028
108
H Iijima, T Aoyama, A Ito, S Yamaguchi, M Nagai, J Tajino, X Zhang, H Kuroki. Effects of short-term gentle treadmill walking on subchondral bone in a rat model of instability-induced osteoarthritis. Osteoarthritis Cartilage 2015; 23(9): 1563–1574 https://doi.org/10.1016/j.joca.2015.04.015
109
W Wang, R Ding, N Zhang, P Hernigou. Subchondral bone cysts regress after correction of malalignment in knee osteoarthritis: comply with Wolff’s law. Int Orthop 2021; 45(2): 445–451 https://doi.org/10.1007/s00264-020-04809-1
110
G Li, J Yin, J Gao, TS Cheng, NJ Pavlos, C Zhang, MH Zheng. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes. Arthritis Res Ther 2013; 15(6): 223–235 https://doi.org/10.1186/ar4405
111
PMB Chan, C Wen, WC Yang, C Yan, K Chiu. Is subchondral bone cyst formation in non-load-bearing region of osteoarthritic knee a vascular problem?. Med Hypotheses 2017; 109: 80–83 https://doi.org/10.1016/j.mehy.2017.09.027
112
H Sumino, S Ichikawa, S Kasama, T Takahashi, H Kumakura, Y Takayama, T Kanda, T Sakamaki, M Kurabayashi. Elevated arterial stiffness in postmenopausal women with osteoporosis. Maturitas 2006; 55(3): 212–218 https://doi.org/10.1016/j.maturitas.2006.02.008
113
S Kamekura, K Hoshi, T Shimoaka, U Chung, H Chikuda, T Yamada, M Uchida, N Ogata, A Seichi, K Nakamura, H Kawaguchi. Osteoarthritis development in novel experimental mouse models induced by knee joint instability. Osteoarthritis Cartilage 2005; 13(7): 632–641 https://doi.org/10.1016/j.joca.2005.03.004
114
J Lieberthal, N Sambamurthy, CR Scanzello. Inflammation in joint injury and post-traumatic osteoarthritis. Osteoarthritis Cartilage 2015; 23(11): 1825–1834 https://doi.org/10.1016/j.joca.2015.08.015
115
K Feng, Y Ge, Z Chen, X Li, Z Liu, X Li, H Li, T Tang, F Yang, X Wang. Curcumin inhibits the PERK-eIF2α-CHOP pathway through promoting SIRT1 expression in oxidative stress-induced rat chondrocytes and ameliorates osteoarthritis progression in a rat model. Oxid Med Cell Longev 2019; 2019: 8574386 https://doi.org/10.1155/2019/8574386
116
HJ Faust, H Zhang, J Han, MT Wolf, OH Jeon, K Sadtler, AN Peña, L Chung, DR Jr Maestas, AJ Tam, DM Pardoll, J Campisi, F Housseau, D Zhou, CO 3rd Bingham, JH Elisseeff. IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis. J Clin Invest 2020; 130(10): 5493–5507 https://doi.org/10.1172/JCI134091
117
JF Xue, ZM Shi, J Zou, XL Li. Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis. Biomed Pharmacother 2017; 89: 1252–1261 https://doi.org/10.1016/j.biopha.2017.01.130
A Mobasheri, C Matta, R Zákány, G Musumeci. Chondrosenescence: definition, hallmarks and potential role in the pathogenesis of osteoarthritis. Maturitas 2015; 80(3): 237–244 https://doi.org/10.1016/j.maturitas.2014.12.003
120
J Shen, Y Abu-Amer, RJ O’Keefe, A McAlinden. Inflammation and epigenetic regulation in osteoarthritis. Connect Tissue Res 2017; 58(1): 49–63 https://doi.org/10.1080/03008207.2016.1208655
121
A Ruscitto, V Scarpa, M Morel, S Pylawka, CJ Shawber, MC Embree. Notch regulates fibrocartilage stem cell fate and is upregulated in inflammatory TMJ arthritis. J Dent Res 2020; 99(10): 1174–1181 https://doi.org/10.1177/0022034520924656
122
B Qiu, X Xu, P Yi, Y Hao. Curcumin reinforces MSC-derived exosomes in attenuating osteoarthritis via modulating the miR-124/NF-κB and miR-143/ROCK1/TLR9 signalling pathways. J Cell Mol Med 2020; 24(18): 10855–10865 https://doi.org/10.1111/jcmm.15714
123
C Wang, J Shen, J Ying, D Xiao, RJ O’Keefe. FoxO1 is a crucial mediator of TGF-β/TAK1 signaling and protects against osteoarthritis by maintaining articular cartilage homeostasis. Proc Natl Acad Sci USA 2020; 117(48): 30488–30497 https://doi.org/10.1073/pnas.2017056117
124
C Lietman, B Wu, S Lechner, A Shinar, M Sehgal, E Rossomacha, P Datta, A Sharma, R Gandhi, M Kapoor, PP Young. Inhibition of Wnt/β-catenin signaling ameliorates osteoarthritis in a murine model of experimental osteoarthritis. JCI Insight 2018; 3(3): e96308 https://doi.org/10.1172/jci.insight.96308
125
J Lu, H Zhang, J Pan, Z Hu, L Liu, Y Liu, X Yu, X Bai, D Cai, H Zhang. Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways. Arthritis Res Ther 2021; 23(1): 142–155 https://doi.org/10.1186/s13075-021-02512-z
126
F Gibertoni, MEL Sommer, MAM Esquisatto, MECD Amaral, CA Oliveira, TAM Andrade, FAS Mendonça, M Jr Santamaria, M Felonato. Evolution of periodontal disease: immune response and RANK/RANKL/OPG system. Braz Dent J 2017; 28(6): 679–687 https://doi.org/10.1590/0103-6440201701407
B Kovács, E Vajda, EE Nagy. Regulatory effects and interactions of the Wnt and OPG-RANKL-RANK signaling at the bone-cartilage interface in osteoarthritis. Int J Mol Sci 2019; 20(18): 4653–4681 https://doi.org/10.3390/ijms20184653
131
TJ Yun, PM Chaudhary, GL Shu, JK Frazer, MK Ewings, SM Schwartz, V Pascual, LE Hood, EA Clark. OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol 1998; 161(11): 6113–6121 https://doi.org/10.4049/jimmunol.161.11.6113
D Frase, C Lee, C Nachiappan, R Gupta, A Akkouch. The inflammatory contribution of B-lymphocytes and neutrophils in progression to osteoporosis. Cells 2023; 12(13): 1744–1759 https://doi.org/10.3390/cells12131744
134
L Rochette, A Meloux, E Rigal, M Zeller, Y Cottin, C Vergely. The role of osteoprotegerin and its ligands in vascular function. Int J Mol Sci 2019; 20(3): 705–724 https://doi.org/10.3390/ijms20030705
135
J Lee, S Lee, CY Lee, HH Seo, S Shin, JW Choi, SW Kim, JC Park, S Lim, KC Hwang. Adipose-derived stem cell-released osteoprotegerin protects cardiomyocytes from reactive oxygen species-induced cell death. Stem Cell Res Ther 2017; 8(1): 195–201 https://doi.org/10.1186/s13287-017-0647-6
136
X Li, L Qin, M Bergenstock, LM Bevelock, DV Novack, NC Partridge. Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts. J Biol Chem 2007; 282(45): 33098–33106 https://doi.org/10.1074/jbc.M611781200
137
M Dutka, R Bobiński, W Wojakowski, T Francuz, C Pająk, K Zimmer. Osteoprotegerin and RANKL-RANK-OPG-TRAIL signalling axis in heart failure and other cardiovascular diseases. Heart Fail Rev 2022; 27(4): 1395–1411 https://doi.org/10.1007/s10741-021-10153-2
138
S Kikuchi, A Wada, Y Kamihara, I Yamamoto, D Kirigaya, K Kunimoto, R Horaguchi, T Fujihira, Y Nabe, T Minemura, NH Dang, T Sato. A novel mechanism for bone loss: platelet count negatively correlates with bone mineral density via megakaryocyte-derived RANKL. Int J Mol Sci 2023; 24(15): 12150–12158 https://doi.org/10.3390/ijms241512150
139
S Theoleyre, Y Wittrant, SK Tat, Y Fortun, F Redini, D Heymann. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev 2004; 15(6): 457–475 https://doi.org/10.1016/j.cytogfr.2004.06.004
140
V Milanova, N Ivanovska, P Dimitrova. TLR2 elicits IL-17-mediated RANKL expression, IL-17, and OPG production in neutrophils from arthritic mice. Mediators Inflamm 2014; 2014: 643406 https://doi.org/10.1155/2014/643406
141
S Hao, J Zhang, B Huang, D Feng, X Niu, W Huang. Bone remodeling serum markers in children with systemic lupus erythematosus. Pediatr Rheumatol Online J 2022; 20(1): 54–60 https://doi.org/10.1186/s12969-022-00717-3
H Hariri, O Kose, A Bezdjian, SJ Daniel, R St-Arnaud. USP53 regulates bone homeostasis by controlling rankl expression in osteoblasts and bone marrow adipocytes. J Bone Miner Res 2023; 38(4): 578–596 https://doi.org/10.1002/jbmr.4778
145
WC Dougall, M Glaccum, K Charrier, K Rohrbach, K Brasel, T De Smedt, E Daro, J Smith, ME Tometsko, CR Maliszewski, A Armstrong, V Shen, S Bain, D Cosman, D Anderson, PJ Morrissey, JJ Peschon, J Schuh. RANK is essential for osteoclast and lymph node development. Genes Dev 1999; 13(18): 2412–2424 https://doi.org/10.1101/gad.13.18.2412
146
X Li, L Cui, W Chen, Y Fang, G Shen, Z Li, B Zhang, L Wu. QiangGuYin modulates the OPG/RANKL/RANK pathway by increasing secretin levels during treatment of primary type I osteoporosis. Evid Based Complement Alternat Med 2021; 2021: 7114139 https://doi.org/10.1155/2021/7114139
147
K Okamoto, T Nakashima, M Shinohara, T Negishi-Koga, N Komatsu, A Terashima, S Sawa, T Nitta, H Takayanagi. Osteoimmunology: the conceptual framework unifying the immune and skeletal systems. Physiol Rev 2017; 97(4): 1295–1349 https://doi.org/10.1152/physrev.00036.2016
148
AE Kearns, S Khosla, PJ Kostenuik. Receptor activator of nuclear factor κB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 2008; 29(2): 155–192 https://doi.org/10.1210/er.2007-0014
149
Y Furuya, H Mera, M Itokazu, S Terai, H Nakamura, S Wakitani, H Yasuda. Induction of chondrogenesis with a RANKL-binding peptide, WP9QY, in vitro and in vivo in a rabbit model. Biochem Biophys Res Commun 2022; 602: 98–104 https://doi.org/10.1016/j.bbrc.2022.03.019
150
B Li, P Wang, J Jiao, H Wei, W Xu, P Zhou. Roles of the RANKL-RANK axis in immunity-implications for pathogenesis and treatment of bone metastasis. Front Immunol 2022; 13: 824117 https://doi.org/10.3389/fimmu.2022.824117
PA van Dam, Y Verhoeven, J Jacobs, A Wouters, W Tjalma, F Lardon, T Van den Wyngaert, J Dewulf, E Smits, C Colpaert, H Prenen, M Peeters, M Lammens, XB Trinh. RANK-RANKL signaling in cancer of the uterine cervix: a review. Int J Mol Sci 2019; 20(9): 2183–2198 https://doi.org/10.3390/ijms20092183
153
T Nakashima, M Hayashi, H Takayanagi. New insights into osteoclastogenic signaling mechanisms. Trends Endocrinol Metab 2012; 23(11): 582–590 https://doi.org/10.1016/j.tem.2012.05.005
154
E González-Suárez, A Sanz-Moreno. RANK as a therapeutic target in cancer. FEBS J 2016; 283(11): 2018–2033 https://doi.org/10.1111/febs.13645
155
AI Lalani, S Zhu, S Gokhale, J Jin, P Xie. TRAF molecules in inflammation and inflammatory diseases. Curr Pharmacol Rep 2018; 4(1): 64–90 https://doi.org/10.1007/s40495-017-0117-y
156
L Galibert, ME Tometsko, DM Anderson, D Cosman, WC Dougall. The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of NF-κB, a member of the TNFR superfamily. J Biol Chem 1998; 273(51): 34120–34127 https://doi.org/10.1074/jbc.273.51.34120
157
X Ma, J Liu, L Yang, B Zhang, Y Dong, Q Zhao. Cynomorium songaricum prevents bone resorption in ovariectomized rats through RANKL/RANK/TRAF6 mediated suppression of PI3K/AKT and NF-κB pathways. Life Sci 2018; 209: 140–148 https://doi.org/10.1016/j.lfs.2018.08.008
Y Duan, YT Su, J Ren, Q Zhou, M Tang, J Li, SX Li. Kidney tonifying traditional Chinese medicine: potential implications for the prevention and treatment of osteoporosis. Front Pharmacol 2023; 13: 1063899 https://doi.org/10.3389/fphar.2022.1063899
160
G Zhen, C Wen, X Jia, Y Li, JL Crane, SC Mears, FB Askin, FJ Frassica, W Chang, J Yao, JA Carrino, A Cosgarea, D Artemov, Q Chen, Z Zhao, X Zhou, L Riley, P Sponseller, M Wan, WW Lu, X Cao. Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med 2013; 19(6): 704–712 https://doi.org/10.1038/nm.3143
161
Y Tang, X Wu, W Lei, L Pang, C Wan, Z Shi, L Zhao, TR Nagy, X Peng, J Hu, X Feng, W Van Hul, M Wan, X Cao. TGF-β1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med 2009; 15(7): 757–765 https://doi.org/10.1038/nm.1979
162
Y Zhong, Y Xu, S Xue, L Zhu, H Lu, C Wang, H Chen, W Sang, J Ma. Nangibotide attenuates osteoarthritis by inhibiting osteoblast apoptosis and TGF-β activity in subchondral bone. Inflammopharmacology 2022; 30(3): 1107–1117 https://doi.org/10.1007/s10787-022-00984-2
163
D Muratovic, DM Findlay, RD Quarrington, X Cao, LB Solomon, GJ Atkins, JS Kuliwaba. Elevated levels of active transforming growth factor β1 in the subchondral bone relate spatially to cartilage loss and impaired bone quality in human knee osteoarthritis. Osteoarthritis Cartilage 2022; 30(6): 896–907 https://doi.org/10.1016/j.joca.2022.03.004
164
W Mu, B Xu, H Ma, J Li, B Ji, Z Zhang, A Amat, L Cao. Halofuginone attenuates osteoarthritis by rescuing bone remodeling in subchondral bone through oral gavage. Front Pharmacol 2018; 9: 269–279 https://doi.org/10.3389/fphar.2018.00269
165
G Zhen, C Wen, X Jia, Y Li, JL Crane, SC Mears, FB Askin, FJ Frassica, W Chang, J Yao, JA Carrino, A Cosgarea, D Artemov, Q Chen, Z Zhao, X Zhou, L Riley, P Sponseller, M Wan, WW Lu, X Cao. Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med 2013; 19(6): 704–712 https://doi.org/10.1038/nm.3143
166
C Lin, Z Chen, D Guo, L Zhou, S Lin, C Li, S Li, X Wang, B Lin, Y Ding. Increased expression of osteopontin in subchondral bone promotes bone turnover and remodeling, and accelerates the progression of OA in a mouse model. Aging (Albany NY) 2022; 14(1): 253–271 https://doi.org/10.18632/aging.203707
167
H Xie, Z Cui, L Wang, Z Xia, Y Hu, L Xian, C Li, L Xie, J Crane, M Wan, G Zhen, Q Bian, B Yu, W Chang, T Qiu, M Pickarski, LT Duong, JJ Windle, X Luo, E Liao, X Cao. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med 2014; 20(11): 1270–1278 https://doi.org/10.1038/nm.3668
168
L Rochette, A Meloux, E Rigal, M Zeller, Y Cottin, C Vergely. The role of osteoprotegerin and its ligands in vascular function. Int J Mol Sci 2019; 20(3): 705 https://doi.org/10.3390/ijms20030705
169
J Zupan, P Vrtačnik, A Cör, G Haring, G Weryha, S Visvikis-Siest, J Marc. VEGF-A is associated with early degenerative changes in cartilage and subchondral bone. Growth Factors 2018; 36(5–6): 263–273 https://doi.org/10.1080/08977194.2019.1570926
170
AR Upton, CA Holding, AA Dharmapatni, DR Haynes. The expression of RANKL and OPG in the various grades of osteoarthritic cartilage. Rheumatol Int 2012; 32(2): 535–540 https://doi.org/10.1007/s00296-010-1733-6
171
S Kwan Tat, N Amiable, JP Pelletier, C Boileau, D Lajeunesse, N Duval, J Martel-Pelletier. Modulation of OPG, RANK and RANKL by human chondrocytes and their implication during osteoarthritis. Rheumatology (Oxford) 2009; 48(12): 1482–1490 https://doi.org/10.1093/rheumatology/kep300
172
G Hashimoto, I Inoki, Y Fujii, T Aoki, E Ikeda, Y Okada. Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165. J Biol Chem 2002; 277(39): 36288–36295 https://doi.org/10.1074/jbc.M201674200
173
DJ Wilkinson, AMD Falconer, HL Wright, H Lin, K Yamamoto, K Cheung, SH Charlton, MDC Arques, S Janciauskiene, R Refaie, KS Rankin, DA Young, AD Rowan. Matrix metalloproteinase-13 is fully activated by neutrophil elastase and inactivates its serpin inhibitor, alpha-1 antitrypsin: implications for osteoarthritis. FEBS J 2022; 289(1): 121–139 https://doi.org/10.1111/febs.16127
174
C Boileau, N Amiable, J Martel-Pelletier, H Fahmi, N Duval, JP Pelletier. Activation of proteinase-activated receptor 2 in human osteoarthritic cartilage upregulates catabolic and proinflammatory pathways capable of inducing cartilage degradation: a basic science study. Arthritis Res Ther 2007; 9(6): R121–R131 https://doi.org/10.1186/ar2329
175
M Xue, H Lin, HPH Liang, K McKelvey, R Zhao, L March, C Jackson. Deficiency of protease-activated receptor (PAR) 1 and PAR2 exacerbates collagen-induced arthritis in mice via differing mechanisms. Rheumatology (Oxford) 2021; 60(6): 2990–3003 https://doi.org/10.1093/rheumatology/keaa701
176
N Amiable, SK Tat, D Lajeunesse, N Duval, JP Pelletier, J Martel-Pelletier, C Boileau. Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts. Bone 2009; 44(6): 1143–1150 https://doi.org/10.1016/j.bone.2009.02.015
177
BN França, LM Gasparoni, ES Rovai, LMB Ambrósio, NF Mendonça, MH Hagy, AH Mendoza, CR Sipert, M Holzhausen. Protease-activated receptor type 2 activation downregulates osteogenesis in periodontal ligament stem cells. Braz Oral Res 2023; 37: e002 https://doi.org/10.1590/1807-3107bor-2023.vol37.0002
178
K Tashiro, H Tada, R Heilker, M Shirozu, T Nakano, T Honjo. Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. Science 1993; 261(5121): 600–603 https://doi.org/10.1126/science.8342023
179
T Nagasawa, H Kikutani, T Kishimoto. Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc Natl Acad Sci USA 1994; 91(6): 2305–2309 https://doi.org/10.1073/pnas.91.6.2305
FM Roversi, MLP Bueno, FV Pericole, STO Saad. Hematopoietic cell kinase (HCK) is a player of the crosstalk between hematopoietic cells and bone marrow niche through CXCL12/CXCR4 axis. Front Cell Dev Biol 2021; 9: 634044 https://doi.org/10.3389/fcell.2021.634044
182
G D’Amato, R Phansalkar, JA Naftaly, X Fan, ZA Amir, Coronado PE Rios, DO Cowley, KE Quinn, B Sharma, KM Caron, A Vigilante, K Red-Horse. Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4. Dev Cell 2022; 57(22): 2517–2532.e6 https://doi.org/10.1016/j.devcel.2022.10.007
183
A Gao, F Yan, E Zhou, L Wu, L Li, J Chen, Y Lei, J Ye. Molecular characterization and expression analysis of chemokine (CXCL12) from Nile tilapia (Oreochromis niloticus). Fish Shellfish Immunol 2020; 104: 314–323 https://doi.org/10.1016/j.fsi.2020.06.003
184
Q Chen, C Zheng, Y Li, S Bian, H Pan, X Zhao, WW Lu. Bone targeted delivery of SDF-1 via alendronate functionalized nanoparticles in guiding stem cell migration. ACS Appl Mater Interfaces 2018; 10(28): 23700–23710 https://doi.org/10.1021/acsami.8b08606
185
CC Bleul, RC Fuhlbrigge, JM Casasnovas, A Aiuti, TA Springer. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 1996; 184(3): 1101–1109 https://doi.org/10.1084/jem.184.3.1101
Y Yang, J Li, W Lei, H Wang, Y Ni, Y Liu, H Yan, Y Tian, Z Wang, Z Yang, S Yang, Y Yang, Q Wang. CXCL12-CXCR4/CXCR7 axis in cancer: from mechanisms to clinical applications. Int J Biol Sci 2023; 19(11): 3341–3359 https://doi.org/10.7150/ijbs.82317
188
A Mousavi. CXCL12/CXCR4 signal transduction in diseases and its molecular approaches in targeted-therapy. Immunol Lett 2020; 217: 91–115 https://doi.org/10.1016/j.imlet.2019.11.007
189
ND Staudt, A Maurer, B Spring, H Kalbacher, WK Aicher, G Klein. Processing of CXCL12 by different osteoblast-secreted cathepsins. Stem Cells Dev 2012; 21(11): 1924–1935 https://doi.org/10.1089/scd.2011.0307
190
SY Cho, M Xu, J Roboz, M Lu, J Mascarenhas, R Hoffman. The effect of CXCL12 processing on CD34+ cell migration in myeloproliferative neoplasms. Cancer Res 2010; 70(8): 3402–3410 https://doi.org/10.1158/0008-5472.CAN-09-3977
191
Y Yan, J Xiong, F Xu, C Wang, Z Zeng, H Tang, Z Lu, Q Huang. SDF-1α/CXCR4 pathway mediates hemodynamics-induced formation of intracranial aneurysm by modulating the phenotypic transformation of vascular smooth muscle cells. Transl Stroke Res 2022; 13(2): 276–286 https://doi.org/10.1007/s12975-021-00925-1
192
G Wang, Y Li, X Meng, X Yang, Y Xiang. The study of targeted blocking SDF-1/CXCR4 signaling pathway with three antagonists on MMPs, type II collagen, and aggrecan levels in articular cartilage of guinea pigs. J Orthop Surg Res 2020; 15(1): 195–202 https://doi.org/10.1186/s13018-020-01646-1
KE McGrath, AD Koniski, KM Maltby, JK McGann, J Palis. Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. Dev Biol 1999; 213(2): 442–456 https://doi.org/10.1006/dbio.1999.9405
195
MP Wescott, I Kufareva, C Paes, JR Goodman, Y Thaker, BA Puffer, E Berdougo, JB Rucker, TM Handel, BJ Doranz. Signal transmission through the CXC chemokine receptor 4 (CXCR4) transmembrane helices. Proc Natl Acad Sci USA 2016; 113(35): 9928–9933 https://doi.org/10.1073/pnas.1601278113
196
CC Chang, JW Liou, KTP Dass, YT Li, SJ Jiang, SF Pan, YC Yeh, HJ Hsu. Internal water channel formation in CXCR4 is crucial for Gi-protein coupling upon activation by CXCL12. Commun Chem 2020; 3(1): 133–145 https://doi.org/10.1038/s42004-020-00383-0
197
L Pawig, C Klasen, C Weber, J Bernhagen, H Noels. Diversity and inter-connections in the CXCR4 chemokine receptor/ligand family: molecular perspectives. Front Immunol 2015; 6: 429–452 https://doi.org/10.3389/fimmu.2015.00429
198
J Imitola, K Raddassi, KI Park, FJ Mueller, M Nieto, YD Teng, D Frenkel, J Li, RL Sidman, CA Walsh, EY Snyder, SJ Khoury. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 2004; 101(52): 18117–18122 https://doi.org/10.1073/pnas.0408258102
199
WW Tong, C Zhang, T Hong, DH Liu, C Wang, J Li, XK He, WD Xu. Silibinin alleviates inflammation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes and has a therapeutic effect on arthritis in rats. Sci Rep 2018; 8(1): 3241–3253 https://doi.org/10.1038/s41598-018-21674-6
200
ME Ziegler, MM Hatch, N Wu, SA Muawad, CC Hughes. mTORC2 mediates CXCL12-induced angiogenesis. Angiogenesis 2016; 19(3): 359–371 https://doi.org/10.1007/s10456-016-9509-6
201
N Kawaguchi, TT Zhang, T Nakanishi. Involvement of CXCR4 in normal and abnormal development. Cells 2019; 8(2): 185–199 https://doi.org/10.3390/cells8020185
202
MA Chetram, V Odero-Marah, CV Hinton. Loss of PTEN permits CXCR4-mediated tumorigenesis through ERK1/2 in prostate cancer cells. Mol Cancer Res 2011; 9(1): 90–102 https://doi.org/10.1158/1541-7786.MCR-10-0235
203
EM García-Cuesta, CA Santiago, J Vallejo-Díaz, Y Juarranz, JM Rodríguez-Frade, M Mellado. The role of the CXCL12/CXCR4/ACKR3 Axis in autoimmune diseases. Front Endocrinol (Lausanne) 2019; 10: 585–601 https://doi.org/10.3389/fendo.2019.00585
204
Y Li, M Xue, X Deng, L Dong, LXT Nguyen, L Ren, L Han, C Li, J Xue, Z Zhao, W Li, Y Qing, C Shen, B Tan, Z Chen, K Leung, K Wang, S Swaminathan, L Li, M Wunderlich, JC Mulloy, X Li, H Chen, B Zhang, D Horne, ST Rosen, G Marcucci, M Xu, Z Li, M Wei, J Tian, B Shen, R Su, J Chen. TET2-mediated mRNA demethylation regulates leukemia stem cell homing and self-renewal. Cell Stem Cell 2023; 30(8): 1072–1090.e10 https://doi.org/10.1016/j.stem.2023.07.001
205
JM Hong, JW Lee, DS Seen, JY Jeong, WK Huh. LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration. Cell Commun Signal 2023; 21(1): 257–280 https://doi.org/10.1186/s12964-023-01261-7
206
É Midavaine, J Côté, P Sarret. The multifaceted roles of the chemokines CCL2 and CXCL12 in osteophilic metastatic cancers. Cancer Metastasis Rev 2021; 40(2): 427–445 https://doi.org/10.1007/s10555-021-09974-2
Q Xu, XC Sun, XP Shang, HS Jiang. Association of CXCL12 levels in synovial fluid with the radiographic severity of knee osteoarthritis. J Investig Med 2012; 60(6): 898–901 https://doi.org/10.2310/JIM.0b013e31825f9f69
209
S Wang, A Mobasheri, Y Zhang, Y Wang, T Dai, Z Zhang. Exogenous stromal cell-derived factor-1 (SDF-1) suppresses the NLRP3 inflammasome and inhibits pyroptosis in synoviocytes from osteoarthritic joints via activation of the AMPK signaling pathway. Inflammopharmacology 2021; 29(3): 695–704 https://doi.org/10.1007/s10787-021-00814-x
210
LM Wright, W Maloney, X Yu, L Kindle, P Collin-Osdoby, P Osdoby. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts. Bone 2005; 36(5): 840–853 https://doi.org/10.1016/j.bone.2005.01.021
211
A Sucur, Z Jajic, M Artukovic, MI Matijasevic, B Anic, D Flegar, A Markotic, T Kelava, S Ivcevic, N Kovacic, V Katavic, D Grcevic. Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells. Arthritis Res Ther 2017; 19(1): 142–158 https://doi.org/10.1186/s13075-017-1337-6
212
X Yu, Y Huang, P Collin-Osdoby, P Osdoby. Stromal cell-derived factor-1 (SDF-1) recruits osteoclast precursors by inducing chemotaxis, matrix metalloproteinase-9 (MMP-9) activity, and collagen transmigration. J Bone Miner Res 2003; 18(8): 1404–1418 https://doi.org/10.1359/jbmr.2003.18.8.1404
213
Y Dong, H Liu, X Zhang, F Xu, L Qin, P Cheng, H Huang, F Guo, Q Yang, A Chen. Inhibition of SDF-1α/CXCR4 signalling in subchondral bone attenuates post-traumatic osteoarthritis. Int J Mol Sci 2016; 17(6): 943–955 https://doi.org/10.3390/ijms17060943
K Kanbe, T Takemura, K Takeuchi, Q Chen, K Takagishi, K Inoue. Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruction of cartilage in osteoarthritis and rheumatoid arthritis. J Bone Joint Surg Br 2004; 86(2): 296–300 https://doi.org/10.1302/0301-620X.86B2.14474
216
C Lin, L Liu, C Zeng, ZK Cui, Y Chen, P Lai, H Wang, Y Shao, H Zhang, R Zhang, C Zhao, H Fang, D Cai, X Bai. Correction to: Activation of mTORC1 in subchondral bone preosteoblasts promotes osteoarthritis by stimulating bone sclerosis and secretion of CXCL12. Bone Res 2019; 7(1): 26–39 https://doi.org/10.1038/s41413-019-0065-8
217
F Wei, DC Moore, L Wei, Y Li, G Zhang, X Wei, JK Lee, Q Chen. Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway. Arthritis Res Ther 2012; 14(4): R177–R188 https://doi.org/10.1186/ar3930
218
L Wei, X Sun, K Kanbe, Z Wang, C Sun, R Terek, Q Chen. Chondrocyte death induced by pathological concentration of chemokine stromal cell-derived factor-1. J Rheumatol 2006; 33(9): 1818–1826
219
P Li, J Deng, X Wei, CT Jayasuriya, J Zhou, Q Chen, J Zhang, L Wei, F Wei. Blockade of hypoxia-induced CXCR4 with AMD3100 inhibits production of OA-associated catabolic mediators IL-1β and MMP-13. Mol Med Rep 2016; 14(2): 1475–1482 https://doi.org/10.3892/mmr.2016.5419
220
J Li, H Chen, L Cai, D Guo, D Zhang, X Zhou, J Xie. SDF-1α promotes chondrocyte autophagy through CXCR4/mTOR signaling axis. Int J Mol Sci 2023; 24(2): 1710–1723 https://doi.org/10.3390/ijms24021710
J Pan, B Wang, W Li, X Zhou, T Scherr, Y Yang, C Price, L Wang. Elevated cross-talk between subchondral bone and cartilage in osteoarthritic joints. Bone 2012; 51(2): 212–217 https://doi.org/10.1016/j.bone.2011.11.030
223
DM Findlay, JS Kuliwaba. Bone-cartilage crosstalk: a conversation for understanding osteoarthritis. Bone Res 2016; 4(1): 16028 https://doi.org/10.1038/boneres.2016.28
224
A Jiang, P Xu, S Sun, Z Zhao, Q Tan, W Li, C Song, H Leng. Cellular alterations and crosstalk in the osteochondral joint in osteoarthritis and promising therapeutic strategies. Connect Tissue Res 2021; 62(6): 709–719 https://doi.org/10.1080/03008207.2020.1870969
225
HJ Qin, T Xu, HT Wu, ZL Yao, YL Hou, YH Xie, JW Su, CY Cheng, KF Yang, XR Zhang, Y Chai, B Yu, Z Cui. SDF-1/CXCR4 axis coordinates crosstalk between subchondral bone and articular cartilage in osteoarthritis pathogenesis. Bone 2019; 125: 140–150 https://doi.org/10.1016/j.bone.2019.05.010
226
J Lei, Y Fu, Y Zhuang, K Zhang. Sema4D aggravated LPS-induced injury via activation of the MAPK signaling pathway in ATDC5 chondrocytes. BioMed Res Int 2020; 2020: 8691534 https://doi.org/10.1155/2020/8691534
227
H Qin, X Zhao, YJ Hu, S Wang, Y Ma, S He, K Shen, H Wan, Z Cui, B Yu. Inhibition of SDF-1/CXCR4 axis to alleviate abnormal bone formation and angiogenesis could improve the subchondral bone microenvironment in osteoarthritis. BioMed Res Int 2021; 2021: 8852574 https://doi.org/10.1155/2021/8852574
228
W Su, G Liu, X Liu, Y Zhou, Q Sun, G Zhen, X Wang, Y Hu, P Gao, S Demehri, X Cao, M Wan. Angiogenesis stimulated by elevated PDGF-BB in subchondral bone contributes to osteoarthritis development. JCI Insight 2020; 5(8): e135446 https://doi.org/10.1172/jci.insight.135446
229
A Hoeben, B Landuyt, MS Highley, H Wildiers, AT Van Oosterom, EA De Bruijn. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 2004; 56(4): 549–580 https://doi.org/10.1124/pr.56.4.3
230
X Lin, RD Bell, SE Catheline, T Takano, A McDavid, JH Jonason, EM Schwarz, L Xing. Targeting synovial lymphatic function as a novel therapeutic intervention for age-related osteoarthritis in mice. Arthritis Rheumatol 2023; 75(6): 923–936 https://doi.org/10.1002/art.42441
231
S Wang, C Zhou, H Zheng, Z Zhang, Y Mei, JA Martin. Chondrogenic progenitor cells promote vascular endothelial growth factor expression through stromal-derived factor-1. Osteoarthritis Cartilage 2017; 25(5): 742–749 https://doi.org/10.1016/j.joca.2016.10.017