Rheumatoid arthritis (RA) is a common autoimmune inflammatory disease causing bone destruction. Although the etiology of RA remains unanswered, it is well known that inflammatory cytokines play key roles. Although biological agents targeting these inflammatory cytokines strongly suppress inflammation as well as bone damages, repair of destructed bone is still challenging. Mesenchymal stem cells (MSCs) are capable to differentiate into osteoblasts and chondrocytes and moreover, they have been reported to possess immunomodulative effects without severe adverse events in patients with graft versus host disease. Recently, we have reported that MSCs produce osteoprotegerin (OPG), a decoy receptor of the receptor activator of NFκB ligand (RANKL) resulting in reduced osteoclastogenesis. We herein demonstrate the promotive effect of inflammatory cytokines on osteoblast differentiation through Wingless-type MMTV integration site family (Wnt) 5a/ receptor tyrosine kinase-like orphan receptor (Ror) 2 signaling pathway. Our results suggest that MSCs is a powerful treatment tool for RA patients to aim suppression of inflammation and bone regeneration in parallel.
The Japanese Society of Inflammation and Regeneration