Bax Targeted by miR-29a Regulates Chondrocyte Apoptosis in Osteoarthritis
Bax Targeted by miR-29a Regulates Chondrocyte Apoptosis in Osteoarthritis
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DOI：
10.1155/2019/1434538
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Zha, Zhengang
中科院分区：
文献类型：
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作者：
Miao, Guiqiang;Zang, Xuehui;Zha, Zhengang
骨关节炎（OA）是一种慢性退行性关节疾病，其中软骨细胞凋亡是负责软骨退行性变。Bax是众所周知的Bcl-2家族的促凋亡蛋白，参与了大量的生理和病理过程。然而，骨性关节炎中Bax在软骨细胞凋亡中的调控机制尚不清楚。在本研究中，我们确定了Bax在人OA和软骨细胞凋亡中的作用。结果显示，Bax在OA患者关节软骨软骨细胞和IL-1处理后培养的软骨细胞样ATDC5细胞中表达上调。通过荧光素酶报告基因检测和western blotting鉴定Bax是miR-29a的直接靶点。miR-29a抑制物对miR-29a的抑制和miR-29a抑制剂的过表达加重了IL-1诱导的ATDC5凋亡。这些数据表明，miR-29a/Bax轴在调节软骨细胞凋亡中起着重要作用，并提示靶向促凋亡蛋白Bax和提高miR-29a的表达水平可能是预防OA发展的潜在途径。
Osteoarthritis (OA) is a chronic degenerative joint disease, where chondrocyte apoptosis is responsible for cartilage degeneration. Bax is a well-known proapoptotic protein of the Bcl-2 family, involved in a large number of physiological and pathological processes. However, the regulation mechanisms of Bax underlying chondrocyte apoptosis in OA remain unknown. In the present study, we determined the role of Bax in human OA and chondrocyte apoptosis. The results showed that Bax was upregulated in chondrocytes from the articular cartilage of OA patients and in cultured chondrocyte-like ATDC5 cells treated by IL-1. Bax was identified to be the direct target of miR-29a by luciferase reporter assay and by western blotting. Inhibition of miR-29a by the mimics protested and overexpression by miR-29a inhibitors aggravated ATDC5 apoptosis induced by IL-1. These data reveal that miR-29a/Bax axis plays an important role in regulating chondrocyte apoptosis and suggest that targeting the proapoptotic protein Bax and increasing expression levels of miR-29a emerge as potential approach for protection against the development of OA.