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骨关节炎中的骨-软骨界面相互作用:潜在途径与未来治疗策略

Bone-cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies.

作者信息

Yuan X L, Meng H Y, Wang Y C, Peng J, Guo Q Y, Wang A Y, Lu S B

机构信息

Institute of Orthopedics, Chinese PLA General Hospital, Fuxing 28# Road, Beijing, China.

Institute of Orthopedics, Chinese PLA General Hospital, Fuxing 28# Road, Beijing, China.

出版信息

Osteoarthritis Cartilage. 2014 Aug;22(8):1077-89. doi: 10.1016/j.joca.2014.05.023. Epub 2014 Jun 10.

Abstract

Currently, osteoarthritis (OA) is considered a disease of the entire joint, which is not simply a process of wear and tear but rather abnormal remodelling and joint failure of an organ. The bone-cartilage interface is therefore a functioning synergistic unit, with a close physical association between subchondral bone and cartilage suggesting the existence of biochemical and molecular crosstalk across the OA interface. The crosstalk at the bone-cartilage interface may be elevated in OA in vivo and in vitro. Increased vascularisation and formation of microcracks associated with abnormal bone remodelling in joints during OA facilitate molecular transport from cartilage to bone and vice versa. Recent reports suggest that several critical signalling pathways and biological factors are key regulators and activate cellular and molecular processes in crosstalk among joint compartments. Therapeutic interventions including angiogenesis inhibitors, agonists/antagonists of molecules and drugs targeting bone remodelling are potential candidates for this interaction. This review summarised the premise for the presence of crosstalk in bone-cartilage interface as well as the current knowledge of the major signalling pathways and molecular interactions that regulate OA progression. A better understanding of crosstalk in bone-cartilage interface may lead to development of more effective strategies for treating OA patients.

摘要

目前,骨关节炎(OA)被认为是一种累及整个关节的疾病,它并非简单的磨损过程,而是一个器官的异常重塑和关节功能衰竭过程。因此,骨 - 软骨界面是一个协同功能单位,软骨下骨与软骨之间紧密的物理联系表明在骨关节炎界面存在生化和分子层面的相互作用。在体内和体外,骨关节炎中骨 - 软骨界面的这种相互作用可能会增强。骨关节炎期间关节内与异常骨重塑相关的血管化增加和微裂纹形成,促进了分子在软骨和骨之间的双向运输。最近的报告表明,几种关键的信号通路和生物因子是关节腔室间相互作用中的关键调节因子,并激活细胞和分子过程。包括血管生成抑制剂、分子激动剂/拮抗剂以及针对骨重塑的药物在内的治疗干预措施是这种相互作用的潜在候选方案。本综述总结了骨 - 软骨界面存在相互作用的前提,以及目前对调节骨关节炎进展的主要信号通路和分子相互作用的认识。更好地理解骨 - 软骨界面的相互作用可能会为治疗骨关节炎患者开发出更有效的策略。

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