PMID- 25515592
OWN - NLM
STAT- MEDLINE
DCOM- 20150817
LR  - 20181113
IS  - 1471-2474 (Electronic)
IS  - 1471-2474 (Linking)
VI  - 15
DP  - 2014 Dec 17
TI  - Histone deacetylase 4 alters cartilage homeostasis in human osteoarthritis.
PG  - 438
LID - 10.1186/1471-2474-15-438 [doi]
LID - 438
AB  - 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-1beta or TNF-alpha, 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.
FAU - Lu, Jingwei
AU  - Lu J
FAU - Sun, Ye
AU  - Sun Y
FAU - Ge, Qiting
AU  - Ge Q
FAU - Teng, Huajian
AU  - Teng H
AD  - Model Animal Research Center of Nanjing University, Nanjing 210061, China. 
      tenghj@nicemice.cn.
FAU - Jiang, Qing
AU  - Jiang Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141217
PL  - England
TA  - BMC Musculoskelet Disord
JT  - BMC musculoskeletal disorders
JID - 100968565
RN  - 0 (Repressor Proteins)
RN  - EC 3.5.1.98 (HDAC4 protein, human)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Arthroplasty, Replacement, Knee/trends
MH  - Cartilage, Articular/*enzymology/pathology
MH  - Cells, Cultured
MH  - Female
MH  - Histone Deacetylases/*biosynthesis
MH  - Homeostasis/*physiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis, Knee/diagnosis/*enzymology/surgery
MH  - Repressor Proteins/*biosynthesis
PMC - PMC4300609
EDAT- 2014/12/18 06:00
MHDA- 2015/08/19 06:00
PMCR- 2014/12/17
CRDT- 2014/12/18 06:00
PHST- 2014/06/29 00:00 [received]
PHST- 2014/11/24 00:00 [accepted]
PHST- 2014/12/18 06:00 [entrez]
PHST- 2014/12/18 06:00 [pubmed]
PHST- 2015/08/19 06:00 [medline]
PHST- 2014/12/17 00:00 [pmc-release]
AID - 1471-2474-15-438 [pii]
AID - 2379 [pii]
AID - 10.1186/1471-2474-15-438 [doi]
PST - epublish
SO  - BMC Musculoskelet Disord. 2014 Dec 17;15:438. doi: 10.1186/1471-2474-15-438.