Human gingival tissue-derived MSC suppress osteoclastogenesis and bone erosion via CD39-adnosine signal pathway in autoimmune arthritis

Abstract

Abstract Bone destruction is one of many severe complications that occurs in patients with rheumatoid arthritis (RA) and current therapies are unable to cure this manifestation. This study aims to determine whether GMSC can directly inhibit osteoclast formation and eventually attenuate osteoclastogenesis and bone erosion in inflammatory milieu. GMSC were co-cultured with osteoclast precursors that had been pretreated with or without the inhibitors of CD39 inhibitor, CD73 inhibitor or adenosine receptors and osteoclast formation were evaluated in vitro. 2×106 GMSC were transferred to CIA mouse and pathology scores, frequency of osteoclasts, and bone erosion in joints were assessed in vivo. We demonstrated that GMSC but not fibroblasts, markedly suppressed human or mice osteoclastogenesis in vitro. GMSC treatment also resulted in a dramatically decreased level of NF-κB p65/p50 in osteoclasts in vitro. Infusion of GMSC to CIA significantly attenuated the severity of arthritis, pathology scores, frequency of osteoclasts, particularly bone erosion, as well as a decreased expression of RANKL in synovial tissues in vivo. Blockade of CD73-CD39-adenosine receptors has significantly abrogated the suppressive ability of GMSC in vitro and therapeutic effect of GMSC on bone erosion during CIA. Thus, GMSC inhibit osteoclast formation in vitro and in vivo partially via CD73-CD39-adenosine signals. Manipulation of GMSC may have a therapeutic implication on rheumatoid arthritis and other bone erosion related diseases.