ADAM-10 Is Involved in Osteoblast Mineralization and Rheumatoid Arthritis-Associated Bone Destruction

Rheumatoid arthritis (RA), a chronic autoimmune condition, causes irreversible bone destruction. A disintegrin and metalloprotease 10 (ADAM-10) has been implicated in inflammatory processes in RA. We investigated the potential role of ADAM-10 in osteoblast mineralization and RA-associated bone destruction. Serum ADAM-10 levels in RA patients were measured by ELISA, and ADAM-10 expression in osteoblasts was assessed by Western blotting. Collagen-induced arthritis (CIA) mice were treated intraperitoneally with the ADAM-10 inhibitor GI254023X (100 mg/kg) for three weeks. Arthritis and bone destruction were evaluated by macroscopic, immunohistochemical, histological, and micro-CT analyses. The effects of ADAM-10 inhibition on primary osteoblast mineralization were also assessed by Alizarin Red S staining. Serum ADAM-10 levels in patients with RA tended to be higher at Stage III of the Steinbrocker classification. In CIA mice, ADAM-10 inhibition attenuated weight loss, paw swelling, and arthritis scores and suppressed bone destruction. ADAM-10 inhibition also significantly reduced Rankl expression in knee joints. Furthermore, the inhibition reversed the suppression of primary osteoblast mineralization induced by TNF-α. Pharmacological inhibition of ADAM-10 attenuated experimental arthritis and bone destruction and improved osteoblast mineralization, suggesting that ADAM-10 may contribute to inflammatory bone destruction in RA.