Surfactin suppresses osteoclastogenesis via the NF-κB signaling pathway, promotes osteogenic differentiation in vitro, and inhibits oestrogen deficiency-induced bone loss in vivo

Abstract

Background: Fractures caused by osteoporosis (OP) are one of the main causes of death in the elderly, bringing a heavy burden to the country and society. The imbalance between osteoblast-mediated osteogenesis and osteoclast-mediated bone resorption is an important cause of OP. Therefore, finding drugs that can regulate this dynamic balance can be an important way to treat osteoporosis. Surfactin is a highly effective biosurfactant derived from Bacillus subtilis and it has been proven to have various pharmacological effects in previous studies, but its effect on bone metabolism remains unknown. Here, we performed a study on the role and mechanism of Surfactin in inhibiting osteoclastogenesis and its possible mechanism as well as the role in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).

Methods: We investigated the effect of Surfactin on osteoclast differentiation and osteogenic differentiation in vitro and in vivo. The effect of Surfactin on the activity of osteoclastogenesis and osteogenesis was verified by CCK-8 assay, quantitative Real-time polymerase chain reaction (qPCR) and Western blotting analysis were used to verify the effect of Surfactin on osteoclast and osteogenic differentiation-specific genes and proteins. The effect of Surfactin on TRAP、ALP activity and mineral deposition was verified by TRAP、ALP and ARS staining. We then used an ovariectomy-induced osteoporosis mice model to observe the effect of Surfactin in vivo.

Results: Surfactin is noncytotoxic to BMMs, RAW264.7, and BMSCs. And it can effectively inhibit osteoclastogenesis and promote osteogenic differentiation. Moreover, we found that Surfactin can inhibit the differentiation of osteoclasts through the NF-κB signaling pathway. Surfactin can also alleviate bone loss in ovariectomy-induced osteoporosis mice.

Conclusions: Our results suggest that Surfactin can inhibit osteoclastogenesis through the NF-κB signaling pathway, promote the osteogenic differentiation of BMSCs, and also can effectively alleviate bone loss in ovariectomy-induced osteoporosis mice.

Keywords: NF-κB; OVX model; Osteoclast differentiation; Osteogenic differentiation; Osteoporosis.