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核因子κβ配体受体激活剂/骨保护素比值升高会加剧骨关节炎中的软骨破坏。

Increased receptor activator of nuclear factor κβ ligand/osteoprotegerin ratio exacerbates cartilage destruction in osteoarthritis .

作者信息

Zeng Ji-Zhou, Wang Zhen-Zhong, Ma Li-Feng, Meng Hai, Yu Hao-Miao, Cheng Wen-Hao, Zhang Ya-Kui, Guo Ai

机构信息

Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China; Department of Orthopedics, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, P.R. China.

Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.

出版信息

Exp Ther Med. 2016 Oct;12(4):2778-2782. doi: 10.3892/etm.2016.3638. Epub 2016 Aug 31.

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage destruction, matrix degradation and bony changes. Subchondral bone alterations in osteoarthritis are associated with cartilage destruction. It has previously been demonstrated that osteoprotegerin (OPG) and receptor activator of nuclear factor κβ ligand (RANKL) mediate this process. The RANKL/OPG ratio is altered in OA chondrocytes compared with normal chondrocytes. In the pathogenesis of OA, abnormal expression levels of matrix metalloproteinase-13 (MMP-13) are secreted by chondrocytes has a vital role in the progression of cartilage erosion. In the present study, the effect of various RANKL/OPG ratios on MMP-13 expression levels was investigated in interleukin-1β-stimulated SW1353 human chondrosarcoma cells. Cell viability was assessed by MTT assay and MMP-13 mRNA and protein expression levels were analyzed by quantitative reverse-transcription-quantitative polymerase chain reaction, ELISA and western blot analyses, respectively. The results demonstrated that an increase in MMP-13 mRNA and protein expression levels was observed with increasing RANKL/OPG ratio. These findings suggest that this mechanism may be used as a novel therapeutic strategy against OA.

摘要

骨关节炎(OA)是一种退行性关节疾病,其特征为进行性软骨破坏、基质降解和骨质改变。骨关节炎中的软骨下骨改变与软骨破坏相关。先前已经证明,骨保护素(OPG)和核因子κβ受体活化因子配体(RANKL)介导了这一过程。与正常软骨细胞相比,OA软骨细胞中的RANKL/OPG比值发生了改变。在OA的发病机制中,软骨细胞分泌的基质金属蛋白酶-13(MMP-13)异常表达水平在软骨侵蚀进展中起重要作用。在本研究中,在白细胞介素-1β刺激的SW1353人软骨肉瘤细胞中研究了不同RANKL/OPG比值对MMP-13表达水平的影响。通过MTT法评估细胞活力,分别通过定量逆转录-定量聚合酶链反应、ELISA和蛋白质印迹分析来分析MMP-13 mRNA和蛋白质表达水平。结果表明,随着RANKL/OPG比值的增加,MMP-13 mRNA和蛋白质表达水平升高。这些发现表明,该机制可用作针对OA的新型治疗策略。

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Origin and function of cartilage stem/progenitor cells in osteoarthritis.骨关节炎中软骨干细胞/祖细胞的起源与功能
Nat Rev Rheumatol. 2015 Apr;11(4):206-12. doi: 10.1038/nrrheum.2014.200. Epub 2014 Dec 23.
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Osteoarthritis: histology and pathogenesis.骨关节炎:组织学与发病机制
Wien Med Wochenschr. 2013 May;163(9-10):212-9. doi: 10.1007/s10354-012-0168-y. Epub 2012 Dec 20.
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Proteases involved in cartilage matrix degradation in osteoarthritis.参与骨关节炎软骨基质降解的蛋白酶。
Biochim Biophys Acta. 2012 Jan;1824(1):133-45. doi: 10.1016/j.bbapap.2011.06.020. Epub 2011 Jul 8.

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