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Glycosylation of DMP1 maintains cranial sutures in mice.

M. Cai,Junhui Li,R. Yue,Zuolin Wang,Yao Sun

Published 2020 in Journal of Oral Rehabilitation

ABSTRACT

BACKGROUND Craniosynostosis, a severe craniofacial developmental disease, can only be treated with surgery currently. Recent studies have shown that proteoglycans are involved in the suture development. For the bone matrix protein, dentin matrix protein 1 (DMP1), glycosylation on the N-terminal of it could generate a functional proteoglycan form of DMP1 during osteogenesis. We identified that the proteoglycan form of DMP1 (DMP1-PG) is highly expressed in mineralization front of suture. But, the potential role of DMP1-PG in suture fusion remain unclear. OBJECTIVE To investigate the role of DMP1-PG in cranial suture fusion and craniofacial bone development. METHODS By using a DMP1 glycosylation site mutation mouse model, DMP1-S89G mice, we compared the suture development in it with control mice. We compared the suture phenotypes, bone formation rate, expression levels of bone formation markers in vivo between DMP1-S89G mice and wild type mice. Meanwhile, cell culture and organ culture were performed to detect the differences of cell differentiation and suture fusion in vitro. Finally, chondroitin sulfate (CHS), as functional component of DMP1-PG, was employed to test whether it could delay the premature suture fusion and the abnormal differentiation of bone mesenchymal stem cells (BMSCs) of DMP1-PG mice. RESULTS DMP1-S89G mice had premature closure of suture and shorter skull size. Lack of DMP1-PG accelerated bone formation in cranial suture. DMP1-PG maintained the essential stemness of BMSCs in suture through blocking the premature differentiation of BMSCs to osteoblasts. Finally, chondroitin sulfate, major component of DMP1-PG, successfully delayed the premature suture fusion by organ culture of skull in vitro. CONCLUSION DMP1-PG could inhibit premature fusion of cranial suture and maintain the suture through regulating the osteogenic differentiation of BMSCs. This article is protected by copyright. All rights reserved.

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