人膝关节骨关节炎中 MMP-13 与 HDAC7 的表达相关性。
Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis.
机构信息
Division of Arthritis Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
出版信息
Mod Rheumatol. 2010 Feb;20(1):11-7. doi: 10.1007/s10165-009-0224-7. Epub 2009 Sep 26.
Abstract
Recent studies suggest that histone deacetylase (HDAC) inhibitors may therapeutically prevent cartilage degradation in osteoarthritis (OA). Matrix metalloproteinase-13 (MMP-13) plays an important role in the pathogenesis of this disease and in the present study we investigated the correlation between HDACs and MMP-13. Comparing the expression of different HDACs in cartilage from OA patients and healthy donors, HDAC7 showed a significant elevation in cartilage from OA patients. High level of HDAC7 expression in OA cartilage was also confirmed by immunohistochemistry. Knockdown of HDAC7 by small interference RNA (siRNA) in SW1353 human chondrosarcoma cells strongly suppressed interleukin (IL)-1-dependent and independent induction of MMP-13 gene expression. In conclusion, elevated HDAC7 expression in human OA may contribute to cartilage degradation via promoting MMP-13 gene expression, suggesting the critical role of MMP-13 in OA pathogenesis.
摘要
最近的研究表明，组蛋白去乙酰化酶（HDAC）抑制剂可能具有治疗骨关节炎（OA）软骨降解的作用。基质金属蛋白酶-13（MMP-13）在该疾病的发病机制中起重要作用，在本研究中我们研究了 HDAC 和 MMP-13 之间的相关性。比较 OA 患者和健康供体软骨中不同 HDAC 的表达，发现 HDAC7 在 OA 患者的软骨中显著升高。免疫组化也证实了 OA 软骨中 HDAC7 的高表达。在人软骨肉瘤 SW1353 细胞中用小干扰 RNA（siRNA）敲低 HDAC7，强烈抑制了白细胞介素（IL）-1 依赖性和非依赖性诱导的 MMP-13 基因表达。总之，人 OA 中 HDAC7 的表达升高可能通过促进 MMP-13 基因表达导致软骨降解，提示 MMP-13 在 OA 发病机制中的关键作用。
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