兰克尔
去卵巢大鼠
二十碳五烯酸
成骨细胞
破骨细胞
间充质干细胞
内分泌学
医学
骨髓
内科学
炎症
细胞生物学
雌激素
化学
体外
生物
多不饱和脂肪酸
生物化学
脂肪酸
病理
受体
激活剂(遗传学)
作者
Z. Wang,Jiaqi Wu,Lijun Li,Kanbin Wang,Xiaoyong Wu,Hongyu Chen,Shi Jiu-jun,Chengwei Zhou,Weijun Zhang,Kai Hang,Deting Xue,Zhijun Pan
标识
DOI:10.1016/j.clnu.2023.07.022
摘要
BackgroundAn imbalance of osteoblasts (OBs) and osteoclasts (OCs) in a chronic inflammatory microenvironment is an important pathological factor leading to osteoporosis. Eicosapentaenoic acid (EPA) has been shown to suppress inflammation in macrophages and adipocytes. However, the effect of EPA on OBs and OCs has yet to be fully elucidated.AimsWe explored the roles of EPA in the differentiation of OBs and OCs, as well as the coupling between OBs and OCs in an inflammatory microenvironment. The effects of EPA on estrogen deficiency-induced osteoporosis were also evaluated.MethodsMouse bone marrow mesenchymal stem cells (mBMSCs) and mouse bone marrow-derived macrophages (mBMMs) were used for in vitro OBs and OCs differentiation. TNF-α was used to create an inflammatory microenvironment. We examined the effects of EPA on osteoblastogenesis in the absence or presence of TNF-α and collect OBs' culture medium as the conditioned medium (CM). Then we examined the effects of EPA and CM on RANKL-induced osteoclastogenesis. The in vivo effects of EPA were determined using an ovariectomized (OVX) mouse model treated with EPA or vehicle.ResultsHigh-dose EPA was shown to promote osteoblastogenesis in an inflammatory environment in vitro, as well as upregulate expression of OBs-specific proteins and genes. ARS and ALP staining also showed that high-dose EPA-treated groups restored mBMSCs' impaired osteogenic capacity caused by TNFa. Mechanistically, EPA suppressed the NF-κB pathway activated by TNF-α in mBMSCs and rescued TNF-α-mediated inhibition of osteoblastogenesis. EPA was also shown to inhibit expression of RANKL and decrease the RANKL/OPG ratio in OBs in an inflammatory environment. CM from TNF-α-stimulated OBs promoted osteoclastogenesis of mBMMs; EPA-treated CM prevented this. In the OVX mouse model, EPA supplementation prevented bone loss in an estrogen deficiency-induced inflammatory environment.ConclusionsEPA was demonstrated for the first time to restore mBMSCs' impaired osteogenic capacity caused by TNFa-induced inflammation and rescue the OBs/OCs balance via regulation of RANKL and OPG expression in OBs. EPA showed a remarkable ability to prevent bone loss in OVX mice, suggesting a potential application of EPA in postmenopausal osteoporosis.
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