Sodium hydrogen sulfide alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via the inhibition of the ubiquitination and degradation of IKB-α

Abstract Background: Although several effective therapies are available for the treatment of postmenopausal osteoporosis (PMO), the most common type of primary osteoporosis (OP). More effective and acceptable drugs to cure postmenopausal osteoporosis were needed. NaHS, the donor of H 2 S, may be one of the drugs to treat PMO, but its role and mechanism are still unclear. Methods： Ovariectomized mice and Sham operation mice, BMMs and RAW264.7 cell lines were used to illustrate the in vivo and in vitro effects of NaHS on the osteoclast differentiation. On the other hand, molecular and histological methods were applied to evaluate the osteoclast differentiation and investigate the in vivo and in vitro mechanism. Results: Phenotypically, NaHS treatment can increase the bone mineral density and bone quality of osteoporosis models induced by ovariectomy (OVX) in mice. Mechanistically, NaHS inhibited the nuclear translocation of p65 by inhibiting the ubiquitination and proteasome degradation of IkB-α. Conclusions: NaHS protects against OVX-induced bone loss by inhibiting osteoclastic bone resorption. It plays an important role in inhibiting osteoclast differentiation and protecting against bone loss in PMO and it is potential for preventing and treating PMO.