Sema4D/Plexin-B1在下颌髁突早期骨关节炎软骨下骨丢失中的作用研究

项目名称： Sema4D/Plexin-B1在下颌髁突早期骨关节炎软骨下骨丢失中的作用研究

项目编号： No.81500875

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 鹿蕾

作者单位： 中国人民解放军第四军医大学

项目金额： 18万元

中文摘要： 软骨下骨丢失是颞下颌关节(TMJ)骨关节炎(OA)早期的重要病理特征。文献及我们最新发表的研究证明：除破骨细胞活动增加外，成骨活性受抑制在TMJ OA早期软骨下骨丢失中发挥重要作用，但其具体调控机制尚不完全清楚。最新发现Sema4D/Plexin-B1主要表达于破骨/成骨细胞，抑制成骨细胞的成骨活动(Nat Med, 2011)，但其在OA中的作用尚不清楚。我们最近在TMJ OA早期首次发现了Sema4D/Plexin-B1在髁突中高表达的特殊形式，说明其在TMJ OA早期软骨下骨骨丢失的成骨抑制中可能有重要作用。本课题拟在此基础上，通过体内外实验明确髁突软骨中高表达的Sema4D/Plexin-B1对软骨下骨成骨活动的作用，确定阻断“Sema4D/Plexin-B1信号”在抑制TMJ OA早期软骨下骨丢失中的作用，最终为延缓TMJ OA发生发展提供新的潜在干预治疗靶点。

中文关键词： 颞下颌关节；骨关节炎；成骨细胞；软骨下骨；Semaphorin4D

英文摘要： Subchondral bone loss is an important pathology feature of early temporomandibular joint (TMJ) osteoarthritis (OA). Previous literature and our group found that besides increase of osteoclastic activity, inhibition of osteoblastic activity plays a significant role in subchondral bone loss of early TMJ OA, but its mechanism is still unclear. It has been lately reported that Sema4D/Plexin-B1 was expressed by osteoclast/osteoblast, which is capable of inhibiting bone formation by osteoblast, but the role of Sema4D/Plexin-B1 in OA is unclear. We found for the first time that Sema4D/Plexin-B1 was up-regulated in the condyle of early TMJ OA, suggesting that the up-regulated Sema4D/Plexin-B1 might play an important role in the subchondral bone loss of early TMJ OA by suppressing osteoblastic activity. The present research aims to study the function of up-regulated Sema4D/Plexin-B1 on bone formation by osteoblast by in vivo and in vitro experiments, to confirm the effect of suppressing Sema4D/Plexin-B1 signaling on inhibiting subchondral bone loss of early TMJ OA, and to investigate new related therapeutic target for the occurrence and development of TMJ OA.

英文关键词： temporomandibular joint;osteoarthritis;osteoblast;subchondral bone;Semaphorin4D