TNFSF11 and rheumatoid arthritis: However, in rat hepatocellular carcinoma-derived cell lines (32), and in human synovial fibroblasts from RA patients (28), myenteric fibroblasts (33), skin fibroblasts (22), and keratinocytes (34), IL-22 induces the activation of mitogen-activated protein kinase (MAPK), a signaling molecule downstream of M-CSF- and RANKL-signaling pathways, which regulates the survival of osteoclast precursors and osteoclast differentiation (35).