SOST Deficiency Aggravates Osteoarthritis in Mice by Promoting Sclerosis of Subchondral Bone
SOST Deficiency Aggravates Osteoarthritis in Mice by Promoting Sclerosis of Subchondral Bone
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SOST 缺乏通过促进软骨下骨硬化加重小鼠骨关节炎
DOI：
10.1155/2019/7623562
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发表时间：
2019-11-11
影响因子：
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通讯作者：
Bai, Ding
中科院分区：
文献类型：
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作者：
Li, Jingyu;Xue, Junjie;Bai, Ding
软骨下骨硬化是骨关节炎（OA）发生发展的起始部分，被认为是由过度的机械负荷引起的，并被证实与其他病理变化相关。硬化蛋白是一种重要的机械应激反应蛋白，由SOST基因编码。它在骨细胞和成熟软骨细胞中表达，已被证明与OA密切相关。然而，SOST基因与OA发生发展的关系和机制尚不清楚。本研究旨在探讨SOST基因在软骨下骨OA发病机制中的作用。在SOST敲除（SOST KO）和野生型（WT）小鼠上建立膝前交叉韧带横断（ACLT）小鼠骨关节炎（OA）模型。采用组织学、显微CT、免疫组化、TRAP染色、Masson染色、甲苯胺蓝染色等方法观察软骨下骨的病理变化和表型改变。结果发现，在OA的发展过程中，硬化蛋白的表达在钙化软骨和矿化软骨下结构中均降低。关节不稳定性诱导了严重的软骨退化表型，与WT小鼠相比，SOST KO小鼠的OARSI评分更高。与WT小鼠相比，OA SOST KO小鼠表现出更高的BMD和BV/TV比值，以及更高的骨重建率和TRAP阳性细胞数，但假手术组之间的差异不显著。结论是sclerostin的缺失通过促进软骨下骨硬化和增加软骨的分解代谢活性而加重小鼠膝关节OA。
As the initial part in the development of osteoarthritis (OA), subchondral bone sclerosis has been considered to be initiated by excess mechanical loading and proven to be correlated to other pathological changes. Sclerostin, which is an essential mechanical stress response protein, is encoded by the SOST gene. It is expressed in osteocytes and mature chondrocytes and has been proven to be closely correlated to OA. However, the relationship and mechanism between the SOST gene and the development of OA remain unclear. The aim of the present study was to investigate the role of the SOST gene in OA pathogenesis in the subchondral bone. A knee anterior cruciate ligament transection (ACLT) mouse osteoarthritis (OA) model on SOST-knockout (SOST KO) and wild-type (WT) mice was established. The pathogenic and phenotypic changes in the subchondral bone were investigated by histology, micro-CT, immunohistochemistry, TRAP staining, Masson staining, and Toluidine blue staining. It was found that sclerostin expression decreased in both the calcified cartilage and mineralized subchondral structures during the development of OA. Joint instability induced a severe cartilage degradation phenotype, with higher OARSI scores in SOST KO mice, when compared to WT mice. SOST KO mice with OA exhibited a higher BMD and BV/TV ratio, as well as a higher rate of bone remodeling and TRAP-positive cell number, when compared to the WT counterparts, but the difference was not significant between the sham-operation groups. It was concluded that loss of sclerostin aggravates knee OA in mice by promoting subchondral bone sclerosis and increasing catabolic activity of cartilage.