Co-culture with synovial tissue in patients with rheumatoid arthritis suppress cell proliferation by regulating MAPK pathway in osteoblasts

There is growing evidence that synovial tissue affects osteoblasts although the mechanisms behind the aberrant bone metabolism in rheumatoid arthritis (RA) are unclear. The aim of this study is to preliminarily establish a co-culture system of rheumatoid arthritis-derived synovial tissue (RAS) and osteoblasts in vitro and to investigate the potential mechanism of RAS on osteoblasts. A consistent volume of approximately 85 mm³ of RAS was cultured isolated and co-cultured with Hfob1.19 cells for up to 21 days. Equal volume of normal synovial tissue (NS) was co-cultured as a control group. Cell proliferation, cell cycle and bone markers were valued and the mechanisms underlying MAPK pathway have been fully delineated. Our findings suggested that co-cultures with RAS exhibited decreased proliferation of Hfob1.19 cells. Moreover, gene and protein expressions of GLUT3 in cells were suppressed, and the cell cycle was also down-regulated. The expressions of related proteins of MAPKs (JNK and p38) signaling pathway were found to be inhibited. Rescue experiments demonstrated that co-cultures with RAS could decrease the growth and cell cycle of Hfob1.19 cells, which were reversed by p-JNK and p-p38 over expression. In conclusion, this study suggested that synovial tissue in patients with RA may negatively regulate osteoblasts proliferation by declining MAPK pathway.