Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis.
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.
Division of Arthritis Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Reiji
R
Higashiyama
Shigeru
S
Miyaki
Satoshi
S
Yamashita
Teruhito
T
Yoshitaka
Görel
G
Lindman
Yoshiaki
Y
Ito
Takahisa
T
Sasho
Kazuhisa
K
Takahashi
Martin
M
Lotz
Hiroshi
H
Asahara
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007150:Immunohistochemistry; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D055815:Young Adult
D015415:Biomarkers; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D034741:RNA, Small Interfering; C012589:trichostatin A; D053509:Matrix Metalloproteinase 13; C543273:HDAC7 protein, human; D006655:Histone Deacetylases