Coordinate down-regulation of cartilage matrix gene expression in Bcl-2 deficient chondrocytes is associated with decreased SOX9 expression and decreased mRNA stability.

Title

Coordinate down-regulation of cartilage matrix gene expression in Bcl-2 deficient chondrocytes is associated with decreased SOX9 expression and decreased mRNA stability.

Creator

Kinkel Mary D; Horton Walter E Jr

Publisher

Journal of cellular biochemistry

Date

2003
2003-04

Description

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.

Subject

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

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

941–953

Issue

5

Volume

88

Citation

Kinkel Mary D; Horton Walter E Jr, “Coordinate down-regulation of cartilage matrix gene expression in Bcl-2 deficient chondrocytes is associated with decreased SOX9 expression and decreased mRNA stability.,” NEOMED Bibliography Database, accessed August 1, 2021, https://neomed.omeka.net/items/show/3032.

Social Bookmarking