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

Vol.20 No.1

Original Article

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

Authors

Reiji Higashiyama^1,2,3 , Shigeru Miyaki¹ , Satoshi Yamashita² , Teruhito Yoshitaka² , G?rel Lindman² , Yoshiaki Ito² , Takahisa Sasho³ , Kazuhisa Takahashi³ , Martin Lotz¹ , Hiroshi Asahara^1,2

Division 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

Received:

3 April 2009

Accepted:

5 August 2009

Published online:

26 September 2009

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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.

Key words

Osteoarthritis - HDAC7 and MMP-13