α-Hemolysin suppresses osteogenesis by inducing lipid rafts accumulation in bone marrow stromal cells
α-Hemolysin suppresses osteogenesis by inducing lipid rafts accumulation in bone marrow stromal cells
复制标题
DOI：
10.1016/j.fct.2020.111689
复制
发表时间：
2020-11-01
影响因子：
4.3
通讯作者：
Yu, Bin
中科院分区：
文献类型：
--
作者：
Liu, Guanqiao;Cheng, Caiyu;Yu, Bin
α-溶血素 (Hla) 被认为是金黄色葡萄球菌 (S. aureus) 毒性的重要毒力因子，但 Hla 影响骨代谢的机制尚不清楚。在这项研究中，2个月大的C57BL/6小鼠用Hla（40μg/kg，腹腔注射）或金黄色葡萄球菌（1 x 10（6）CFU/ml，100μl静脉注射）治疗，并存在或不存在甲基-β-环糊精（M beta CD）（300mg/kg，腹腔注射）。 MicroCT 分析显示，Hla 治疗后第 2 周至第 4 周，小鼠股骨干骺端出现进行性骨质流失，并伴有成骨细胞减少和破骨细胞增加。此外，Hla在体内和体外刺激Caveolin-1的表达，激活骨髓干细胞（BMSC）细胞膜上的脂筏积累，并抑制BMSC的成骨。用 M beta CD 破坏脂筏或用大豆黄酮抑制 Caveolin-1 可以阻断 Hla 对 BMSC 成骨的不利影响。重要的是，用 M beta CD 治疗小鼠可以挽救 Hla 诱导的成骨细胞损失和破骨细胞生成增加以及金黄色葡萄球菌感染诱导的骨质流失。总之，我们证明 Hla 通过抑制成骨直接诱导骨破坏，并通过刺激破骨细胞生成间接诱导骨破坏，并且脂筏可能介导 Hla 和金黄色葡萄球菌对成骨和骨形成的有害影响。
alpha-hemolysin (Hla) is considered an essential virulent factor for Staphylococcus aureus (S. aureus) toxicity, the mechanism by which Hla affect bone metabolism is poorly understood. In this study, 2-month-old C57BL/6 mice were treated with Hla (40 mu g/kg, i.p.) or S. aureus (1 x 10(6) CFU/ml, 100 mu l i.v.) with the presence or absence of methyl-beta-cyclodextrin (M beta CD) (300 mg/kg, i.p.). MicroCT analysis showed progressive bone loss from week 2 to week 4 after Hla treatment, accompanied by a decreased osteoblasts and increased osteoclasts in femoral metaphysis in mice. Further, Hla stimulated the expression of Caveolin-1 in vivo and in vitro, activated lipid rafts accumulation in cell membrane of bone marrow stmmal cells (BMSCs), and suppressed osteogenesis of BMSCs. Destruction of lipid rafts with M beta CD or inhibition of Caveolin-1 with Daidzein blocked the detrimental effect of Hla on osteogenesis of BMSCs. Importantly, treating mice with M beta CD rescued the loss of osteoblasts and increased osteoclastogenesis induced by Hla as well as the bone loss induced by S. aureus infection. Together, we demonstrate that Hla induces bone destruction directly by suppressing osteogenesis and indirectly by stimulating osteoclastogenesis, and that lipid rafts may mediate the detrimental effect of Hla and S. aureus on osteogenesis and bone formation.