Glycosylation of dentin matrix protein 1 is critical for fracture healing via promoting chondrogenesis
Hui Xue1, Dike Tao1, Yuteng Weng1, Qiqi Fan1, Shuang Zhou1, Ruilin Zhang1, Han Zhang2, Rui Yue3, Xiaogang Wang4(), Zuolin Wang1(), Yao Sun1()
1. Department of Implantology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China 2. School & Hospital of Stomatology, Tongji University, Shanghai 200072, China 3. School of Life Sciences and Technology, Tongji University, Shanghai 200072, China 4. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing 100083, China
Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.
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