PDF(Pubmed)
Abstract：
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that exerts physiological effects via G protein-coupled receptor 120 (GPR120). In our previous studies, we figured out the inhibitory effects of DHA on TNF-α (Tumor necrosis factor-α)-induced osteoclastogenesis via GPR120 in vivo. Moreover, DHA directly suppressed RANKL expression in osteoblasts via GPR120 in vitro. In this study, we generated bone marrow chimeric mice using GPR120 deficient mice (GPR120-KO) to study the inhibitory effects of DHA on bone resorption and osteoclast formation. Bone marrow cells of wild-type (WT) or GPR120-KO mice were transplanted into irradiated recipient mice, which were WT or GPR120 deficient mice. The resulting chimeric mice contained stromal cells from the recipient and bone marrow cells, including osteoclast precursors, from the donor. These chimeric mice were used to perform a series of histological and microfocus computed tomography (micro-CT) analyses after TNF-α injection for induction of osteoclast formation with or without DHA. Osteoclast number and bone resorption were found to be significantly increased in chimeric mice, which did not express GPR120 in stromal cells, compared to chimeric mice, which expressed GPR120 in stromal cells. DHA was also found to suppress specific signaling pathways. We summarized that DHA suppressed TNF-α-induced stromal-dependent osteoclast formation and bone resorption via GPR120.
摘要：
二十二碳六烯酸(DHA)是通过G蛋白偶联受体120(GPR120)发挥生理作用的ω-3脂肪酸。在我们之前的研究中,我们发现DHA在体内通过GPR120对TNF-α（肿瘤坏死因子-α）诱导的破骨细胞生成的抑制作用。此外，DHA通过GPR120在体外直接抑制成骨细胞中RANKL的表达。在这项研究中,我们使用GPR120缺陷小鼠(GPR120-KO)产生骨髓嵌合小鼠,以研究DHA对骨吸收和破骨细胞形成的抑制作用.将野生型（WT）或GPR120-KO小鼠的骨髓细胞移植到受照射的受体小鼠中，它们是WT或GPR120缺陷小鼠。产生的嵌合小鼠含有来自受体和骨髓细胞的基质细胞，包括破骨细胞前体，来自捐赠者。在注射TNF-α后，使用这些嵌合小鼠进行一系列组织学和微焦点计算机断层扫描（micro-CT）分析，以诱导有或没有DHA的破骨细胞形成。在嵌合小鼠中发现破骨细胞数量和骨吸收显著增加，在基质细胞中不表达GPR120，与嵌合小鼠相比，在基质细胞中表达GPR120。还发现DHA抑制特定的信号通路。我们总结了DHA通过GPR120抑制TNF-α诱导的基质依赖性破骨细胞形成和骨吸收。
