Role of SHOX2 in the development of intervertebral disc degeneration
Role of SHOX2 in the development of intervertebral disc degeneration
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SHOX2在椎间盘退变发展中的作用
DOI：
10.1002/jor.23140
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发表时间：
2017
影响因子：
2.8
通讯作者：
Leung Victor Y. L.
中科院分区：
文献类型：
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作者：
Ye Fubiao;Wang Hua;Zheng Zhaomin;He Peiheng;Sribastav Shilabant Sen;Wang Huafeng;Wang Jianru;Liu Hui;Leung Victor Y. L.
腰椎间盘退变是引起下腰痛的最常见原因，影响80%的人的一生，给他们带来沉重的经济负担。许多因素已被证明参与IVD变性。在这项研究中，我们研究了身材矮小同源框2（SHOX 2）在IVD变性发展中的作用。首先检测SHOX 2在人椎间盘退变不同阶段的表达，然后探讨SHOX 2对髓核细胞增殖和凋亡的影响，最后评价SHOX 2对髓核细胞产生细胞外基质的影响。结果显示，与房颤组织相比，SHOX 2主要在NP中表达，其表达随着人IVD退变程度的加重而降低。TNF-α处理导致NP细胞中SHOX 2 mRNA、蛋白表达和启动子活性的剂量和时间依赖性降低。沉默SHOX 2基因可抑制NP细胞增殖并诱导NP细胞凋亡。最后，SHOX 2沉默导致NP细胞中聚集蛋白聚糖和胶原II表达降低，沿着ECM降解酶MMP 3和ADAMTS-5增加。以上结果提示，SHOX 2在IVD退变过程中起重要作用，可能是IVD退变的保护因子。其确切作用及机制有待进一步研究。© 2017骨科研究学会。出版社：Wiley Periodicals，Inc. J Orthop Res 35：1047-1057，2017。
Intervertebral disc (IVD) degeneration is the most common cause of low back pain, which affect 80% of the population during their lives, with heavy economic burden. Many factors have been demonstrated to participate in IVD degeneration. In this study, we investigated the role ofshort stature homeobox 2(SHOX2) in the development of IVD degeneration. First, we detected the expression of SHOX2 in different stages of human IVD degeneration; then explored the role of SHOX2 on nucleus pulposus (NP) cells proliferation and apoptosis, finally we evaluated the effect of SHOX2 on the production of extracellular matrix in NP cells. Results showed that the expression of SHOX2 is mainly in NP compared with AF tissues, its expression decreased with the severity of human IVD degeneration. TNF‐α treatment led to dose‐ and time‐dependent decrease in SHOX2 mRNA, protein expression and promoter activity in NP cells. The silencing of SHOX2 inhibited NP cells proliferation and induced NP cells apoptosis. Finally, SHOX2 silencing led to decreased aggrecan and collagen II expression, along with increased ECM degrading enzymes MMP3 and ADAMTS‐5 in NP cells. In summary, our results indicated that SHOX2 plays an important role in the process of IVD degeneration, and might be a protective factor for IVD degeneration. Further studies are required to confirm its exact role, and clarify the mechanism. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1047–1057, 2017.