Estrogen deficiency and inflammation are known to play important roles in bone metabolism and occurrence of osteoporosis. Monotropein as an iridoid 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-1β, inhibited the nuclear translocation of p65 and NF-κB P50, and down-regulated the phosphorylation of NF-κB p65 and IKK, indicating that monotropein could attenuate inflammatory impairment to MC3T3-E1 cells by suppressing the activation of NF-κB pathway. All these results suggest that monotropein may prove to be a promising candidate for the prevention and treatment of inflammatory bone loss.

已知雌激素缺乏和炎症在骨代谢和骨质疏松症的发生中起重要作用。据报道，monotropein作为一种类环烷苷，可以减少雌激素缺乏引起的骨质流失，并抑制LPS引起的RAW 264.7巨噬细胞的炎症反应。然而，在慢性炎性疾病中，monotropein对骨质流失的影响仍不清楚。在本研究中发现，通过增强卵巢切除术和LPS联合作用，骨质疏松小鼠中，monotropein可以显着抑制骨量减少，并通过增强骨形成和阻断炎症细胞因子的分泌而改善骨微结构。我们的体外实验进一步证明，monotropein能够提高碱性磷酸酶（ALP）的增殖和活性，LPS损伤成骨细胞MC3T3-E1细胞中骨基质矿化和骨基质蛋白骨桥蛋白（OPN）的表达。此外，monotropein可以显着降低IL-6和IL-1β的产生，抑制p65和NF-κBP50的核转运，并下调NF-κBp65和IKK的磷酸化，表明monotropein可以减轻炎症损伤。通过抑制NF-κB途径的激活来抑制MC3T3-E1细胞的凋亡。所有这些结果表明，monotropein可能被证明是预防和治疗炎症性骨丢失的有前途的候选者。并下调NF-κBp65和IKK的磷酸化，表明单糖原蛋白可以通过抑制NF-κB途径的激活来减轻对MC3T3-E1细胞的炎性损伤。所有这些结果表明，monotropein可能被证明是预防和治疗炎症性骨丢失的有前途的候选者。并下调NF-κBp65和IKK的磷酸化，表明单糖原蛋白可以通过抑制NF-κB途径的激活来减轻对MC3T3-E1细胞的炎性损伤。所有这些结果表明，monotropein可能被证明是预防和治疗炎症性骨丢失的有前途的候选者。