title: Histone deacetylase 4 alters cartilage homeostasis in human osteoarthritis.
abstract: BACKGROUND
  Osteoarthritis (OA) is the most common degenerative joint disorder, and a major cause of pain and disability among the elderly. Histone deacetylase 4 (HDAC4) has been shown to be a key regulator of chondrocyte hypertrophy during skeletogenesis. The aims of present study were to investigate the expression of HDAC4 in normal and OA cartilage and its potential roles during OA pathogenesis.
  
  
  METHODS
  The knee cartilage specimen (a total of 18, 12 female and 6 male) were obtained from primary OA patients undergoing total knee arthroplasty (TKA) and normal donors. By using immunohistochemistry staining, we detected the expression patterns of HDAC4 in OA cartilage and normal cartilage respectively. To assess the potential roles of HDAC4, HDAC4 expression in human chondrosarcoma cells (SW1353) was down-regulated by transfecting small interference RNA (siRNA), thereafter, cells were treated with IL-1β or TNF-α, and the expressions of several matrix-degrading enzymes and anabolic factors were examined by using quantitative PCR.
  
  
  RESULTS
  The expression of HDAC4 was observed in the OA cartilage, whereas it was barely detected in the normal cartilage. The extent of HDAC4 expression had a statistically negative correlation with OA severity. We further explored that the reduction of HDAC4 level led to a significant repression of proinflammation cytokines induced up-regulated expressions of matrix-degrading enzymes (MMP1 (Matrix metalloproteinase 1), MMP3 (Matrix metalloproteinase 3) , MMP13 (Matrix metalloproteinase 13), ADAMTS4 (aggrecanase 1) and ADAMTS5 (aggrecanase 2)) in SW1353 in vitro. Moreover, knockdown of HDAC4 inhibited the expression of some anabolic genes (such as aggrecan).
  
  
  CONCLUSIONS
  In this study, our findings suggest that the abnormal expression of HDAC4 in osteoarthritic cartilage might be implicated in promoting catabolic activity of chondrocyte, which is associated with OA pathogenesis. Thus, our findings give a new insight into the mechanism of articular cartilage damage, and indicate that HDAC4 might be a potential target for the therapeutic interventions of OA.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Lu
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
authors.forename: Qiting
authors.initials: Q
authors.lastname: Ge
authors.affiliation: Model Animal Research Center of Nanjing University, Nanjing 210061, China. tenghj@nicemice.cn.
authors.forename: Huajian
authors.initials: H
authors.lastname: Teng
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019645:Arthroplasty, Replacement, Knee / Q000639:trends; D002358:Cartilage, Articular / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D006655:Histone Deacetylases / Q000096:biosynthesis*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000201:enzymology* / Q000601:surgery; D012097:Repressor Proteins / Q000096:biosynthesis*
chemical_list: D012097:Repressor Proteins; C400300:HDAC4 protein, human; D006655:Histone Deacetylases