Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis

Reiji HigashiyamaDivision of Arthritis Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;Department of Systems BioMedicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan;Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

Shigeru MiyakiDivision of Arthritis Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

Satoshi YamashitaDepartment of Systems BioMedicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan

Teruhito YoshitakaDepartment of Systems BioMedicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan

Görel LindmanDepartment of Systems BioMedicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan

Yoshiaki ItoDepartment of Systems BioMedicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan

Takahisa SashoDepartment of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

Kazuhisa TakahashiDepartment of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

Martin LotzDivision of Arthritis Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

Hiroshi AsaharaDivision of Arthritis Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;Department of Systems BioMedicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, JapanCorrespondence[email protected]

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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.

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Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis

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Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis

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