Regulation of chondrocyte functions by transient receptor potential cation channel V6 in osteoarthritis
Regulation of chondrocyte functions by transient receptor potential cation channel V6 in osteoarthritis
复制标题
骨关节炎中瞬时受体电位阳离子通道 V6 对软骨细胞功能的调节
DOI：
10.1002/jcp.25770
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发表时间：
2017-11-01
影响因子：
5.6
通讯作者：
Ye, Tianwen
中科院分区：
文献类型：
--
作者：
Song, Tengfei;Ma, Jun;Ye, Tianwen
瞬时受体电位香草酸（TRPV）通道的作用是维持骨骼中钙信号传导和钙代谢的动态平衡。本研究的目的是确定 TRPV6 在软骨细胞调节中的潜在作用。通过蛋白质印迹分析源自骨关节炎（OA）大鼠模型和 OA 患者膝关节的关节软骨中 TRPV6 的表达水平。使用微计算和组织学分析在 6 个月和 12 个月大时检查 TRPV6 敲除小鼠膝关节的骨结构和骨关节炎变化。此外，为了研究TRPV6对软骨细胞胞外基质分泌、基质降解酶的释放、细胞增殖和凋亡的影响，我们分别用编码靶向TRPV6的shRNA和编码TRPV6的慢病毒构建体降低和增加软骨细胞中TRPV6的表达。结果显示，OA大鼠模型中TRPV6表达水平显着下调。 TRPV6 基因敲除小鼠表现出严重的骨关节炎变化，包括软骨颤动、烧伤和蛋白聚糖损失。此外，TRPV6的缺陷明显影响软骨细胞的功能，例如细胞外基质的分泌、基质降解酶的释放、细胞增殖和凋亡。综上所述，我们的结果表明 TRPV6 通道作为软骨保护因子，参与 OA 的发病机制。
Transient receptor potential vanilloid (TRPV) channels function to maintain the dynamic balance of calcium signaling and calcium metabolism in bones. The goal of this study was to determine the potential role of TRPV6 in regulation of chondrocytes. The level of TRPV6 expression was analyzed by western blot in articular cartilage derived from the knee joints of osteoarthritis (OA) rat models and OA patients. Bone structure and osteoarthritic changes in the knee joints of TRPV6 knockout mice were examined using micro-computed and histological analysis at the age of 6 and 12 months old. Furthermore, to investigate the effects of TRPV6 on chondrocyte extracellular matrix secretion, the release of matrix degrading enzymes, cell proliferation, and apoptosis, we decreased and increased TRPV6 expression in chondrocytes with lentiviral constructs encoding shRNA targeting TRPV6 and encoding TRPV6, respectively. The results showed that the level of TRPV6 expression in an OA rat model was markedly down-regulated. TRPV6 knockout mice showed severe osteoarthritis changes, including cartilage fibrillation, eburnation, and loss of proteoglycans. In addition, deficiency of TRPV6 clearly affected chondrocyte function, such as extracellular matrix secretion, the release of matrix degrading enzymes, cell proliferation, and apoptosis. Taken together, our results implicated that TRPV6 channel, as a chondro-protective factor, was involved in the pathogenesis of OA.