Exp Mol Med.  2010 Aug;42(8):565-573. 10.3858/emm.2010.42.8.057.

Synovial fluid of patients with rheumatoid arthritis induces alpha-smooth muscle actin in human adipose tissue-derived mesenchymal stem cells through a TGF-beta1-dependent mechanism

• Song HY
• Kim MY
• Kim KH
• Lee IH
• Shin SH
• Lee JS
• Kim JH

• KMID: 1104383
• DOI: http://doi.org/10.3858/emm.2010.42.8.057

Abstract

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-beta1 (TGF-beta1) is a secreted protein that promotes differentiation of synovial fibroblasts to alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts to repair the damaged joints. Synovial fluid from patients with RA (RA-SF) induced expression of alpha-SMA in human adipose tissue-derived mesenchymal stem cells (hASCs). RA-SF-induced alpha-SMA expression was abrogated by immunodepletion of TGF-beta1 from RA-SF with anti-TGF-beta1 antibody. Furthermore, pretreatment of hASCs with the TGF-beta type I receptor inhibitor SB431542 or lentiviral small hairpin RNA-mediated silencing of TGF-beta type I receptor expression in hASCs blocked RA-SF-induced alpha-SMA expression. Small interfering RNA-mediated silencing of Smad2 or adenoviral overexpression of Smad7 (an inhibitory Smad isoform) completely inhibited RA-SF-stimulated alpha-SMA expression. These results suggest that TGF-beta1 plays a pivotal role in RA-SF-induced differentiation of hASCs to alpha-SMA-positive cells.

Keyword

mesenchymal stem cells; rheumatoid arthritis; synovial fluid; transforming growth factor beta1; alpha-smooth muscle actin

MeSH Terms

Actins/*metabolism
Adipose Tissue/*cytology
Arthritis, Rheumatoid/*metabolism
Humans
Mesenchymal Stem Cells/*metabolism
Receptors, Lysophosphatidic Acid/metabolism
Signal Transduction
Smad2 Protein/metabolism
Stress Fibers/metabolism
Synovial Fluid/*metabolism
Transforming Growth Factor beta1/*metabolism