Signaling "cross-talk" between TGF-beta1 and ECM signals in chondrocytic cells.
The objective of this investigation was to clarify how the integrin pathway modulates downstream effectors of the TGF-beta1 pathway in chondrocytic cell signaling. The levels of Smad2 and Smad3 phosphorylation upon TGF-beta1 or alpha2beta1 integrin (Type II collagen) stimulation were analyzed by Western blotting techniques. Cellular response was determined by quantitation of procollagen gene expression. Stimulation of cells with TGF-beta1 and Type II collagen led to rapid phosphorylation of Smad2 and 3 with phosphorylation peaking between 15 min and 1 h. Combined stimulation led to a synergistic increase in the phosphorylation of Smad2 and Smad3. Type II collagen gene expression paralleled Smad phosphorylation. Type II collagen modulates the TGF signaling cascade involving Smad2 and Smad3 leading to an increase in Type II collagen transcription. Therefore, we conclude that TGF-beta1 and integrin stimuli interact prior to Smad2 and 3 phosphorylation in the cytoplasm of chondrocytic cells and regulates the expression of ECM components in chondrocytes.
Schneiderbauer
Michaela M
MM
Department of Orthopedics, 200 First Street SW, Mayo Clinic, Rochester, MN 55905, USA.
Dutton
Charyl M
CM
Scully
Sean P
SP
D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D024043:Collagen Type II; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D038982:Integrin alpha2beta1; D016023:Integrins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1