Boeravinone B, a natural rotenoid, inhibits osteoclast differentiation through modulating NF-κB, MAPK and PI3K/Akt signaling pathways
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Osteoporosis is a major public health concern, which requiresnovel therapeutic strategies to prevent or mitigate bone loss. Natural compounds have attracted attention as potential therapeuticagents due to their safety and efficacy. In this study, weinvestigated the regulatory activities of boeravinone B (BOB), anatural rotenoid isolated from the medicinal plant Boerhaviadiffusa, on the differentiation of osteoclasts and mesenchymalstem cells (MSCs), the two main cell components responsiblefor bone remodeling. We found that BOB inhibited osteoclastdifferentiation and function, as determined by TRAP stainingand pit formation assay, with no significant cytotoxicity. Furthermore,our results showing that BOB ameliorates ovariectomyinducedbone loss demonstrated that BOB is also effective invivo. BOB exerted its inhibitory effects on osteoclastogenesis bydownregulating the RANKL/RANK signaling pathways, includingNF-κB, MAPK, and PI3K/Akt, resulting in the suppression ofosteoclast-specific gene expression. Further experiments revealedthat, at least phenomenologically, BOB promotes osteoblast differentiationof bone marrow-derived MSCs but inhibits their differentiationinto adipocytes. In conclusion, our study demonstratesthat BOB inhibits osteoclastogenesis and promotes osteoblastogenesisin vitro by regulating various signaling pathways. Thesefindings suggest that BOB has potential value as a novel therapeuticagent for the prevention and treatment of osteoporosis.
Abstract
Osteoporosis is a major public health concern, which requiresnovel therapeutic strategies to prevent or mitigate bone loss. Natural compounds have attracted attention as potential therapeuticagents due to their safety and efficacy. In this study, weinvestigated the regulatory activities of boeravinone B (BOB), anatural rotenoid isolated from the medicinal plant Boerhaviadiffusa, on the differentiation of osteoclasts and mesenchymalstem cells (MSCs), the two main cell components responsiblefor bone remodeling. We found that BOB inhibited osteoclastdifferentiation and function, as determined by TRAP stainingand pit formation assay, with no significant cytotoxicity. Furthermore,our results showing that BOB ameliorates ovariectomyinducedbone loss demonstrated that BOB is also effective invivo. BOB exerted its inhibitory effects on osteoclastogenesis bydownregulating the RANKL/RANK signaling pathways, includingNF-κB, MAPK, and PI3K/Akt, resulting in the suppression ofosteoclast-specific gene expression. Further experiments revealedthat, at least phenomenologically, BOB promotes osteoblast differentiationof bone marrow-derived MSCs but inhibits their differentiationinto adipocytes. In conclusion, our study demonstratesthat BOB inhibits osteoclastogenesis and promotes osteoblastogenesisin vitro by regulating various signaling pathways. Thesefindings suggest that BOB has potential value as a novel therapeuticagent for the prevention and treatment of osteoporosis.
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