Regulatory role of mesenchymal stem cells in osteoclast differentiation

Mesenchymal stem cells (MSCs) are adult totipotent cells that can differentiate into osteoblasts and chondrocytes. Based on this property, they are theoretically useful for treatment of bone erosive diseases such as rheumatoid arthritis (RA) including joint repair. MSCs constitutively produce a variety of cytokines and growth factors, which explain their immunomodulatory effects on inflammatory cells. Recent clinical trials have shown their efficacy in graft versus host disease. However, whether MSCs can be used for treatment of RA remains unclear. Especially, there is a need to identify and characterize all soluble mediators, i.e., the “trophic effects” ” ” ” of MSCs on the differentiation of osteoclasts, which are involved in bone destruction in RA. We reported previously that human MSCs suppress osteoclast differentiation by constitutive production of osteoprotegerin, the decoy receptor of RANKL. Our results further highlighted the potential usefulness of MSCs for RA treatment by preventing the progression of bone damage by inhibiting osteoclast differentiation. The next step in the clinical application of MSCs includes identifying the best tissue source for these cells and refinement of RA treatment methodology. Recent studies have confirmed that MSCs are important for both bone and synovial tissue homeostasis acting as precursors of osteoblasts and chondrocytes and through their trophic effects. Taken together, MSCs are a hopeful tool to combat joint inflammation and enhance joint repair in RA, ensuring complete cure of this devastating disease.