Histone deacetylase 4 alters cartilage homeostasis in human osteoarthritis

BMC Musculoskeletal Disorders

Qing Jiang³  Huajian Teng¹  Qiting Ge¹  Ye Sun¹  Jingwei Lu² 

[1] Model Animal Research Center of Nanjing University, Nanjing 210061, China;Medical School of Nanjing University, Nanjing 210093, China;The Center of Diagnosis and Treatment for Joint Disease, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China

关键词: Homeostasis;    Catabolism;    Chondrocyte;    HDAC4;    Osteoarthritis;   

Others  :  1090411
DOI  :  10.1186/1471-2474-15-438

 received in 2014-06-29, accepted in 2014-11-24,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Lu et al.; licensee BioMed Central.

【 图 表 】

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