Synovial fluid of patients with rheumatoid arthritis induces α-smooth muscle actin in human adipose tissue-derived mesenchymal stem cells through a TGF-β1-dependent mechanism

• Published in: Experimental & molecular medicine 2010, 42(8), , pp.565-573
• Main Authors: Song, Hae Young, Kim, Min Young, Kim, Kyung Hye, Lee, Il Hwan, Shin, Sang Hun, Lee, Jung Sub, Kim, Jae Ho
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Medical Biochemistry; Molecular Medicine; Original; Stem Cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2010.42.8.057

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-β1 (TGF-β1) is a secreted protein that promotes differentiation of synovial fibroblasts to α-smooth muscle actin (α-SMA)-positive myofibroblasts to repair the damaged joints. Synovial fluid from patients with RA (RA-SF) induced expression of α-SMA in human adipose tissue-derived mesenchymal stem cells (hASCs). RA-SF-induced α-SMA expression was abrogated by immunodepletion of TGF-β1 from RA-SF with anti-TGF-β1 antibody. Furthermore, pretreatment of hASCs with the TGF-β type I receptor inhibitor SB431542 or lentiviral small hairpin RNA-mediated silencing of TGF-β type I receptor expression in hASCs blocked RA-SF-induced α-SMA expression. Small interfering RNA-mediated silencing of Smad2 or adenoviral overexpression of Smad7 (an inhibitory Smad isoform) completely inhibited RA-SF-stimulated α-SMA expression. These results suggest that TGF-β1 plays a pivotal role in RA-SF-induced differentiation of hASCs to α-SMA-positive cells.