Monotropein attenuates ovariectomy and LPS-induced bone loss in mice and decreases inflammatory impairment on osteoblast through blocking activation of NF-κB pathway

Estrogen deficiency and inflammation are known to play important roles in bone metabolism and occurrence of osteoporosis. Monotropein as an iri doi d glycoside is reported to decrease estrogen deficiency-induced bone loss and inhibit inflammatory response in LPS-induced RAW 264.7 macrophages. However, the effect of monotropein on bone loss in chronic inflammatory conditions remains unclear. It was found in the present study that monotropein significantly inhibited bone mass reduction and improved bone micro-architectures by enhancing bone formation and blocking increased secretion of inflammatory cytokines in osteoporotic mice induced by combined ovariectomy and LPS. Our in vitro experiment further demonstrated that monotropein was able to increase the proliferation and activity of alkaline phosphatase (ALP), bone matrix mineralization and the expression of bone matrix protein osteopontin (OPN) in osteoblastic MC3T3-E1 cells injured by LPS. In addition, monotropein significantly decreased the production of IL-6 and IL-1 beta, inhibited the nuclear translocation of p65 and NF-kappa B P50, and down-regulated the phosphorylation of NF-kappa B p65 and IKK, indicating that monotropein could attenuate inflammatory impairment to MC3T3-E1 cells by suppressing the activation of NF-kappa B pathway. All these results suggest that monotropein may prove to be a promising candidate for the prevention and treatment of inflammatory bone loss.