Distinguishing the proapoptotic and antiresorptive functions of risedronate in murine osteoclasts: Role of the Akt pathway and the ERK/Bim axis

摘要: Objective Nitrogen-containing bisphosphonates are one of the most successful therapeutics for osteoporosis. The aim this study was to elucidate functional mechanism typical nitrogen-containing bisphosphonates, risedronate. Methods Osteoclasts generated from murine bone marrow macrophages were treated with risedronate in vitro, and its effects on apoptosis bone-resorbing activity examined. action examined by gene induction constitutively active Akt-1 MEK-1, deletion Bim. Bim−/− mice, which osteoclasts resistant apoptosis, analyzed radiographically, biochemically, histologically. Results Risedronate induced osteoclast through mitochondria-dependent pathway an increased expression Bim, proapoptotic effect suppressed Bim MEK-1 introduction. In contrast, risedronate-induced suppression resorption completely reversed inducing Akt-1, but not or These results suggested that regulated ERK/Bim axis Akt pathway, respectively, both risedronate. Although response administration treatment mineral density mice at a level equivalent wild-type mice. Conclusion Our findings indicate antiresorptive vivo is mainly mediated apoptosis.