Coordinate down-regulation of cartilage matrix gene expression in Bcl-2 deficient chondrocytes is associated with decreased SOX9 expression and decreased mRNA stability.
Aggrecans; Animals; C-Type; Cell Line; Chondrocytes/*physiology; Collagen Type II/genetics/metabolism; Dactinomycin; Down-Regulation; Extracellular Matrix Proteins/analysis/genetics/*metabolism; Gene Expression Regulation; Glycoproteins/analysis/genetics/*metabolism; High Mobility Group Proteins/genetics/*metabolism; Lectins; Matrilin Proteins; Messenger/analysis/biosynthesis; Polymerase Chain Reaction/methods; Proteoglycans/genetics/metabolism; Proto-Oncogene Proteins c-bcl-2/deficiency/genetics/*physiology; Rats; RNA; RNA Stability; Signal Transduction; SOX9 Transcription Factor; Transcription Factors/genetics/*metabolism; Transfection
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.
Kinkel Mary D; Horton Walter E Jr
Journal of cellular biochemistry
2003
2003-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jcb.10442" target="_blank" rel="noreferrer noopener">10.1002/jcb.10442</a>
Age-related expression patterns of Bag-1 and Bcl-2 in growth plate and articular chondrocytes.
Aging/*metabolism; Animals; Articular/cytology/*metabolism; Carrier Proteins/genetics/*metabolism; Cartilage; Cell Division/physiology; Cells; Chondrocytes/cytology/*metabolism; Cultured; DNA-Binding Proteins; Gene Expression Regulation; Growth Plate/*metabolism; Inbred C57BL; Mice; Proto-Oncogene Proteins c-bcl-2/*metabolism; Tissue Distribution; Transcription Factors
Aging cartilage displays increased chondrocyte apoptosis and decreased responsiveness of chondrocytes to growth factors. The molecular mechanisms responsible for these changes have not been identified. Bag-1 is a Bcl-2-binding protein that promotes cell survival, interacts with a diverse group of cellular proteins, and may integrate multiple pathways involved in controlling cell survival, growth, and phenotype. Bcl-2 is important for maintaining chondrocyte phenotype and delaying terminal differentiation and apoptosis of chondrocytes. Comparatively little is known about the role of Bag-1 in cartilage. Here we show that both growth plate and articular chondrocytes in the mouse express the Bag-1 protein. In the growth plate, Bag-1 expression is prominent in the late proliferative and prehypertrophic chondrocytes, displaying a pattern similar to what has been reported for Bcl-2. Further, the expression of both Bcl-2 and Bag-1 declines with age in the articular cartilage. Growth assays demonstrate that knocking down Bag-1 expression causes a decrease in growth rate. These results suggest that Bag-1 is involved in the regulation of chondrocyte phenotype and cartilage aging.
Kinkel Mary D; Yagi Rieko; McBurney Denise; Nugent Ashleigh; Horton Walter E Jr
The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology
2004
2004-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/ar.a.20063" target="_blank" rel="noreferrer noopener">10.1002/ar.a.20063</a>