Boeravinone B, a natural rotenoid, inhibits osteoclast differentiation through modulating NF-κB, MAPK and PI3K/Akt signaling pathways

Abstract

Osteoporosis is a major public health concern, which requires novel therapeutic strategies to prevent or mitigate bone loss. Natural compounds have attracted attention as potential therapeutic agents due to their safety and efficacy. In this study, we investigated the regulatory activities of boeravinone B (BOB), a natural rotenoid isolated from the medicinal plant Boerhavia diffusa , on the differentiation of osteoclasts and mesenchymal stem cells (MSCs), the two main cell components responsible for bone remodeling. We found that BOB inhibited osteoclast differentiation and function, as determined by TRAP staining and pit formation assay, with no significant cytotoxicity. Furthermore, our results showing that BOB ameliorates ovariectomy-induced bone loss demonstrated that BOB is also effective in vivo . BOB exerted its inhibitory effects on osteoclastogenesis by downregulating the RANKL/RANK signaling pathways, including NF-κB, MAPK, and PI3K/Akt, resulting in the suppression of osteoclast-specific gene expression. Further experiments revealed that, at least phenomenologically, BOB promotes osteoblast differentiation of bone marrow-derived MSCs but inhibits their differentiation into adipocytes. In conclusion, our study demonstrates that BOB inhibits osteoclastogenesis and promotes osteoblastogenesis in vitro by regulating various signaling pathways. These findings suggest that BOB has potential value as a novel therapeutic agent for the prevention and treatment of osteoporosis.

Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection

“…The extent and magnitude of the inflammatory response is related to disease severity and clinical outcomes [ 306 , 307 , 308 ]. During this inflammatory pathogenesis process, bacterial pathogens activate several cellular signaling cascades, including RANK/RANKL signaling pathways (e.g., NF-κB, MAPK, and PI3K), where upregulation activates osteoclastogenesis and, ultimately, bone resorption [ 309 ]. Monocytes and macrophages are osteoclast precursor cells and fuse to form osteoclasts, thereby contributing a critical role in facilitating bone resorption [ 310 ].…”