Glycosylation of dentin matrix protein 1 is critical for fracture healing via promoting chondrogenesis

Abstract

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.

Key words： fracture; extracellular matrix; dentin matrix protein 1; proteoglycan; cartilage

Acknowledgements

This study was supported by Key Project of Chinese National Programs for Research and Development (No. 2016YFC1102075, Yao Sun), National Natural Science Foundation of China (Nos. 81470715, 81771043, 81822012, Yao Sun; 81770873, 81722031, Xiaogang Wang; 81670962, Zuolin Wang), Shanghai Health System (No. 2017 BR009, Yao Sun), Tongji University (Nos. TJ15042119036 and TJ2000219143, Zuolin Wang), and Chinese Universities Scientific Fund (No. kx0200020173386, Rui Yue). We would like to appreciate Dr. Chunlin Qin (College of Dentistry, Texas A&M University) for providing the DMP1-N antibody and assistance. We thank Qigang Wang Group, School of Chemical Science and Engineering, Tongji University for providing biomechanical testing machine. We would also like to thank Xiaojuan Yang, Gongchen Li, and Mengmeng Liu for their help in revising the paper.

Compliance with ethics guidelines

Hui Xue, Dike Tao, Yuteng Weng, Qiqi Fan, Shuang Zhou, Ruilin Zhang, Han Zhang, Rui Yue, Xiaogang Wang, Zuolin Wang, and Yao Sun declare no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-019-0693-9 and is accessible for authorized users.

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