Department of Stomatology, The First Affiliated Hospital of Qiqihaer Medical University, Qiqihaer, Heilongjiang, 161041, China; Department of Implantology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, China.
Department of Implantology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, China.
Biochem Biophys Res Commun. 2020 Jun 11;526(4):1125-1130. doi: 10.1016/j.bbrc.2020.04.020. Epub 2020 Apr 21.
The regeneration of bone defects is necessary for the successful healing. During the process of healing, callus plays crucial roles in providing the stable bone-reconstruction environment. The callus is consisted of various large molecules including collagen proteins, non-collagen proteins and proteoglycans (PGs), which are involved in maintaining mechanical strength and interacting with cytokines and grow factors in the injury sites. Recently, our data have found that the PG form of Dentin Matrix Protein 1 (DMP1-PG), which is a newly identified PG, was richly expressed in the bone defect sites. Previous researches have demonstrated the special role of DMP1-PG in chondrogenesis and endochondral ossification, however, the knowledge about the role of DMP1-PG in bone defect repair is still limited. To further detect the potential function of DMP1-PG in the defect healing, we employed a bone defect intramembranous ossification model using the glycosylation site mutant DMP1-PG (S-G, S89G-DMP1) mouse. The morphologic changes of calluses and abnormal expression levels of osteogenesis genes were displayed in the injury sites in S89G-DMP1 mice. In addition, impaired BMP-Smad signaling pathway was observed due to the deficiency of DMP1-PG. Collectively, our findings indicated that the DMP1-PG is one of key proteoglycans in the process of defect healing via regulating the osteogenesis.
骨缺损的再生对于成功愈合是必要的。在愈合过程中，骨痂在提供稳定的骨重建环境方面起着至关重要的作用。骨痂由各种大分子组成，包括胶原蛋白、非胶原蛋白和蛋白聚糖（PGs），它们参与维持机械强度，并与损伤部位的细胞因子和生长因子相互作用。最近，我们的数据发现，牙本质基质蛋白 1（DMP1-PG）的 PG 形式，即一种新鉴定的 PG，在骨缺损部位丰富表达。先前的研究表明 DMP1-PG 在软骨生成和软骨内骨化中具有特殊作用，然而，关于 DMP1-PG 在骨缺损修复中的作用的知识仍然有限。为了进一步检测 DMP1-PG 在缺损愈合中的潜在功能，我们使用糖基化位点突变 DMP1-PG（S-G，S89G-DMP1）小鼠建立了骨缺损膜内成骨模型。在 S89G-DMP1 小鼠的损伤部位显示出骨痂的形态变化和成骨基因的异常表达水平。此外，由于 DMP1-PG 的缺乏，观察到 BMP-Smad 信号通路受损。总之，我们的研究结果表明，DMP1-PG 是通过调节成骨作用参与缺损愈合过程的关键蛋白聚糖之一。
