D-mannose attenuates lipopolysaccharide-induced osteolysis via CPT1A-Mediated lipid metabolic regulation in macrophages
D-mannose attenuates lipopolysaccharide-induced osteolysis via CPT1A-Mediated lipid metabolic regulation in macrophages
复制标题
D-甘露糖通过 CPT1A 介导的巨噬细胞脂质代谢调节减轻脂多糖诱导的骨溶解
DOI：
10.1016/j.bbrc.2021.10.020
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发表时间：
2021
影响因子：
3.1
通讯作者：
Jun Wang
中科院分区：
文献类型：
--
作者：
Zhenzhen Zhang;Xueman Zhou;Jiaqi Liu;Yingcheng Zheng;Yange Wu;Wenke Yang;Yating Yi;Jin Liu;Jun Wang
炎症性骨溶解通常与促炎巨噬细胞的激活和随之而来的过度破骨细胞形成有关。新出现的证据表明，靶向巨噬细胞脂质代谢的药剂或药物可能在预防和治疗骨溶解方面具有潜力。d-甘露糖作为一种天然存在的代谢调节剂，对减轻骨质减少和炎症有很强的作用。然而，甘露糖对骨溶解是否有效，代谢机制是否起作用仍有待研究。本研究通过LPS诱导的炎性溶骨小鼠模型和LPS诱导的炎性巨噬细胞培养系统，我们发现-甘露糖通过逆转LPS诱导的促炎巨噬细胞的激活来减轻炎性溶骨和抑制过度的破骨细胞生成。机械上，d-甘露糖恢复lps抑制的cpt1转录，促进巨噬细胞脂质代谢。用依托莫西（一种CPT1A抑制剂）治疗可消除d-甘露糖对lps处理的巨噬蛋白的体外作用，并消除其对体内溶骨的保护作用。总之，我们的研究结果表明-甘露糖通过控制巨噬细胞中cpt1a介导的脂质代谢来减弱lps诱导的骨溶解。我们的研究结果揭示了未被认识到的d-甘露糖作为抗炎症性骨溶解的有效干预的利用，并提供了通过治疗靶向巨噬细胞脂质代谢来控制炎症情景的证据。
Inflammatory osteolysis is usually linked to the activation of proinflammatory macrophage and the consequent excessive osteoclast formation. Emerging evidence indicates that agents or drugs targeting lipid metabolism in macrophages might be potential in the prevention and treatment of osteolysis.d-mannose, as a natural-existed metabolic regulator, exerts strong effects on attenuating osteopenia and inflammation. However, whetherd-mannose is therapeutically effective on osteolysis and whether a metabolic mechanism counts for the effect remain to be addressed. Here, by using anin vivolipopolysaccharide (LPS)-induced inflammatory osteolysis mouse model as well as anin vitroLPS-induced inflammatory macrophage culture system, we show thatd-mannose attenuates inflammatory osteolysis and inhibits excessive osteoclastogenesis by reversing the LPS-induced activation of proinflammatory macrophage. Mechanically,d-mannose recovers LPS-suppressedCpt1atranscription and promotes lipid metabolism of macrophage. Treatment with etomoxir, an inhibitor of CPT1A, abolishes the effects ofd-mannose on LPS-treated macrophagein vitroand eliminates its protection against osteolysisin vivo. Collectively, our results imply thatd-mannose attenuates LPS-induced osteolysis by manipulating CPT1A-mediated lipid metabolism in macrophages. Our results disclose the unrecognized utilization ofd-mannose as an effective intervention against inflammatory osteolysis and provide evidence to manage inflammatory scenarios by therapeutically targeting lipid metabolism in macrophage.