Department of Physiology, University of Pretoria, Pretoria 0001, South Africa.
School of Food and Nutrition, Massey Institute of Food Science and Technology, Massey University, Palmerston North 4442, New Zealand; Institute for Food, Nutrition and Well-being, University of Pretoria, Pretoria 0001, South Africa; Department of Human Nutrition, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Mar;1864(3):281-289. doi: 10.1016/j.bbalip.2018.12.009. Epub 2018 Dec 19.
Bone is a dynamic tissue that is constantly remodelled by bone resorbing osteoclasts and bone forming osteoblasts, respectively. A breakdown in the remodelling process underlies several bone diseases such as osteoporosis. Unsaturated fatty acids (UFAs) have been shown to have beneficial effects on bone health. However, the mechanism of action of UFAs in bone remains unclear. Free fatty acid receptor 4 (FFAR4) is expressed in bone cells and preferentially binds ω-3 and ω-7 UFAs. Therefore, we sought to determine if FFAR4 influenced the action of different classes of UFAs in bone cells. FFAR4 and potential signalling pathways, β-arrestin 2 (βarr2) and G, were silenced in RAW264.7 murine macrophages (pre-osteoclasts) and MC3T3-E1 murine pre-osteoblasts. Cell differentiation, activation of signalling pathways and expression of regulatory genes were evaluated. The ω-3 UFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and the ω-7 UFA, palmitoleic acid (PLA), were shown to require the FFAR4/βarr2 signalling pathway to inhibit osteoclast differentiation in RAW264.7 murine macrophages. The ω-6 UFA, arachidonic acid, and the ω-9 UFA, oleic acid (OA), were shown to inhibit osteoclast formation but did not use FFAR4. DHA, EPA, PLA and OA enhanced osteoblast signalling through the FFAR4/βarr2 signalling axis. This study reveals that FFAR4/βarr2 signalling may mediate the bone protective effects of different classes of UFAs in osteoclasts and osteoblasts.
骨骼是一种动态组织，分别由破骨细胞和成骨细胞进行骨吸收和骨形成来重塑。几种骨骼疾病（如骨质疏松症）的基础就是重塑过程的破坏。不饱和脂肪酸（UFAs）已被证明对骨骼健康有益。然而，UFAs 在骨骼中的作用机制仍不清楚。游离脂肪酸受体 4（FFAR4）在骨细胞中表达，并优先结合 ω-3 和 ω-7 UFAs。因此，我们试图确定 FFAR4 是否影响不同类别 UFAs 在骨细胞中的作用。FFAR4 和潜在的信号通路，β-arrestin 2（βarr2）和 G，在 RAW264.7 鼠巨噬细胞（前破骨细胞）和 MC3T3-E1 鼠前成骨细胞中被沉默。评估了细胞分化、信号通路的激活和调节基因的表达。研究表明，ω-3 UFAs，二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）以及 ω-7 UFA，棕榈油酸（PLA），需要 FFAR4/βarr2 信号通路来抑制 RAW264.7 鼠巨噬细胞中的破骨细胞分化。ω-6 UFA，花生四烯酸，和 ω-9 UFA，油酸（OA），被证明抑制破骨细胞形成，但不使用 FFAR4。DHA、EPA、PLA 和 OA 通过 FFAR4/βarr2 信号轴增强成骨细胞信号。这项研究揭示了 FFAR4/βarr2 信号可能介导不同类别 UFAs 在破骨细胞和成骨细胞中的骨保护作用。
