Adrenomedullin inhibits osteoclast differentiation through the suppression of receptor activator of nuclear factor-κB ligand-induced nuclear factor-κB activation in glucocorticoid-induced osteoporosis

The current study aimed to improve the understanding on the association between adrenomedullin and osteoporosis in mice with glucocorticoid-induced osteoporosis. Bone resorption and osteoporosis-associated indexes, including maximum load, stiffness, energy to failure, ultimate strength, elastic modulus, post-yield displacement and post-yield displacement, in mice with osteoporosis were analyzed in order to evaluate the effect of adrenomedullin. The receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation was investigated subsequent to treatment with adrenomedullin in vitro. The results demonstrated that adrenomedullin significantly improved bone mass loss, density, bone strength and osteoporosis disease in the mice with glucocorticoid-induced osteoporosis. In addition, adrenomedullin markedly improved the osteoporosis-associated NFATc1, TRAP, OSCAR and c-Fos expression levels. Furthermore, the current findings indicated that RANKL-mediated osteoclast differentiation was suppressed in vitro and in vivo. Notably, the data revealed that adrenomedullin significantly improved the osteoporotic symptoms through inhibition of RANKL-induced NF-κB activation in glucocorticoid-induced osteoporosis. In conclusion, adrenomedullin serves an essential role in the progression of glucocorticoid-induced osteoporosis, regulating the bone mass loss, density and strength through the NF-κB signaling pathway.