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Coordinate down‐regulation of cartilage matrix gene expression in Bcl‐2 deficient chondrocytes is associated with decreased SOX9 expression and decreased mRNA stability
Author(s) -
Kinkel Mary D.,
Horton Walter E.
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10442
Subject(s) - aggrecan , chondrocyte , sox9 , microbiology and biotechnology , cartilage , cartilage oligomeric matrix protein , messenger rna , type ii collagen , chemistry , apoptosis , gene expression , hyaline cartilage , matrix (chemical analysis) , transcription factor , biology , gene , anatomy , osteoarthritis , biochemistry , articular cartilage , pathology , medicine , alternative medicine , chromatography
The anti‐apoptotic protein Bcl‐2 has been shown to function in roles unrelated to apoptosis in a variety of cell types. We have previously reported that loss of Bcl‐2 expression alters chondrocyte morphology and modulates aggrecan expression via an apoptosis‐independent pathway. Here we show that Bcl‐2 is required for chondrocytes to maintain expression of a variety of cartilage‐specific matrix proteins. Using quantitative, real‐time PCR, we demonstrate that Bcl‐2‐deficient chondrocytes coordinately down‐regulate genes coding for hyaline cartilage matrix proteins including collagen II, collagen IX, aggrecan, and link protein. The decrease in steady‐state level of these mRNA transcripts results, in part, from decreased mRNA stability in Bcl‐2‐deficient chondrocytes. Transcriptional regulation is also likely involved because chondrocytes with decreased Bcl‐2 levels show decreased expression of SOX9, a transcription factor necessary for expressing the major cartilage matrix proteins. In contrast, chondrocytes constitutively expressing Bcl‐2 have a stable phenotype when subjected to loss of serum factor signaling. These cells maintain high levels of SOX9, as well as the SOX9 targets collagen II and aggrecan. These results suggest that Bcl‐2 is involved in a pathway important for maintaining a stable chondrocyte phenotype. J. Cell. Biochem. 88: 941–953, 2003. © 2003 Wiley‐Liss, Inc.