GMSCs suppress osteoclastogenesis and bone erosion in collagen-induced arthritis through curbing NF-KB and RANKL signals (THER5P.900)

Abstract

Abstract Osteoclasts are responsible for bone destruction in rheumatoid arthritis (RA) and gingiva-derived mesenchymal stem cells (GMSCs) can inhibit experimental collagen-induced-arthritis (CIA) model. This study aims to determine if GMSCs also suppress osteolastogenesis and bone erosion in CIA. Osteoclasts were induced from bone-marrow CD11b+ cells with RANKL and macrophage colony-stimulating factor (M-CSF), and assessed with tartrate-resistant acid phosphatase (TRAP) staining. Human osteoclasts were induced from human CD14+ cells. GMSCs were generated and added to cultures with different ratios with CD11b+ or CD14+ cells. NF-κB activation was determined by western blot. 2×106 GMSCs or fibroblast cells were adoptively transferred to DBA1/J mice on day 14 after immunization with CII/CFA. CIA onset and severity were monitored and bone erosion was examined by HE staining. We showed that GMSCs but not fibroblast cells completely suppressed osteoclastogenesis in vitro for human and mice cells. GMSCs injected after immunization and before of onset of CIA significantly suppressed disease development. Treatment with GMSCs dramatically decreased the levels of NF-κB p65/p50 in osteoclasts in vitro and P65/50 and RANKL expression by synovial tissues in vivo. These results suggest that the manipulation of GMSCs may have therapeutic effects on rheumatoid arthritis and other bone erosion related diseases.