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Negative Regulation of Chondrocyte Differentiation by Transcription Factor AP‐2α
Author(s) -
Huang Zhengmin,
Xu Haiming,
Sandell Linda
Publication year - 2004
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2004.19.2.245
Subject(s) - chondrocyte , aggrecan , chondrogenesis , microbiology and biotechnology , cellular differentiation , biology , type ii collagen , gene expression , cartilage , sox9 , transcription factor , proteoglycan , chemistry , extracellular matrix , gene , genetics , anatomy , medicine , pathology , osteoarthritis , articular cartilage , alternative medicine
This study investigated the role of transcription factor AP‐2α in chondrocyte differentiation in vitro. AP‐2α mRNA declined during differentiation, and overexpression of AP‐2α inhibited differentiation. The results demonstrated that AP‐2α plays a negative role in chondrocyte differentiation. Introduction: Transcription factor AP‐2α has been detected in growth plate and articular chondrocytes and has been shown to regulate cartilage matrix gene expression in vitro. However, the precise functional role of AP‐2α in chondrocyte differentiation is not known. In this study, we assessed the expression and the function of AP‐2α in chondrocyte differentiation of ATDC5 cells. Materials and Methods: Chondrocyte differentiation of ATDC5 cells was induced with insulin or transforming growth factor β (TGF‐β) . Proteoglycan production was assessed by alcian blue staining, and expression levels of chondrocyte marker genes and AP‐2 gene family were determined by quantitative real time reverse transcriptase‐polymerase chain reaction (RT‐PCR). Overexpression of AP‐2α in ATDC5 cells was accomplished by retroviral infection. Infected cells were selected for G418 resistance and pooled for further analysis. Results and Conclusions: Quantitative real time RT‐PCR analysis showed that among the four members of the AP‐2 gene family, AP‐2α mRNA was the most abundant. AP‐2α mRNA levels progressively declined during the differentiation induced by either insulin or TGF‐β treatment. Retroviral expression of AP‐2α in ATDC5 cells prevented the formation of cartilage nodules, suppressed the proteoglycan production, and inhibited the expression of type II collagen, aggrecan , and type X collagen . Expression profile analysis of key transcription factors involved in chondrogenesis showed that overexpression of AP‐2α maintained the expression of Sox9 but suppressed the expression of Sox5 and Sox6 . Taken together, we provide, for the first time, molecular and cellular evidence suggesting that AP‐2α is a negative regulator of chondrocyte differentiation.