Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Texas Health Science Center at San Antonio, San Antonio, TX -78229-3900, USA.
J Cell Mol Med. 2009 Aug;13(8B):1833-44. doi: 10.1111/j.1582-4934.2009.00649.x.
Beneficial effects of n-3 fatty acids (FA) on bone mineral density (BMD) have been reported in mice, rats and human beings, but the precise mechanisms involved have not been described. This study used the Fat-1 mouse, a transgenic model that synthesizes n-3 FA from n-6 FA to directly determine if outcome of bone health were correlated with n-3 FA. Ovariectomized (Ovx) and sham operated wild-type (WT) and Fat-1 mice were fed an AIN-93M diet containing 10% corn oil for 24 weeks. BMD was analysed by dual energy x-ray absorptiometry. Fat-1 Ovx mice exhibited significantly lower level of osteotropic factors like receptor activator of NF-kappaB ligand and tartrate-resistant acid phosphatase (TRAP)5b in serum and higher BMD in distal femoral metaphysis, proximal tibial metaphysis, femoral diaphysis and lumbar vertebra as compared to WT Ovx mice. LPS-stimulated bone marrow (BM) cells from Fat-1 Ovx mice produced significantly lower level of pro-inflammatory cytokines like tumour necrosis factor-alpha, interleukin (IL)-1-beta, IL-6 and higher level of anti-inflammatory cytokines like IL-10, IFN-gamma and higher level of nitric oxide as compared to BM cells from WT Ovx mice. LPS-stimulated COX-II activity as well as NF-kappaB activation in BM cells from Fat-1 Ovx mice was significantly less as compared to BM cells from WT Ovx mice. Furthermore, Fat-1 BM cells generated significantly less number of TRAP osteoclast-like cells as compared to WT BM cells. In conclusion, we offer further insight into the mechanisms involved in preventing the BMD loss in Ovx mice by n-3 FA using a Fat-1 transgenic mouse model.
已有研究报道，n-3 脂肪酸（FA）对小鼠、大鼠和人类的骨密度（BMD）有益，但涉及的确切机制尚未描述。本研究使用 Fat-1 小鼠，这是一种从 n-6 FA 合成 n-3 FA 的转基因模型，以直接确定骨骼健康的结果是否与 n-3 FA 相关。对去卵巢（Ovx）和假手术野生型（WT）及 Fat-1 小鼠进行喂养，饲料为含 10%玉米油的AIN-93M 饮食，共 24 周。采用双能 X 射线吸收法分析 BMD。与 WT Ovx 小鼠相比，Fat-1 Ovx 小鼠的血清中骨形成因子如 NF-κB 配体受体激活剂和抗酒石酸酸性磷酸酶（TRAP）5b 的水平明显较低，而远端股骨干骺端、近端胫骨干骺端、股骨骨干和腰椎的 BMD 则明显较高。与 WT Ovx 小鼠的 BM 细胞相比，Fat-1 Ovx 小鼠的 LPS 刺激的 BM 细胞产生的促炎细胞因子如肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6 的水平明显较低，抗炎细胞因子如 IL-10、IFN-γ和一氧化氮的水平则明显较高。与 WT Ovx 小鼠的 BM 细胞相比，Fat-1 Ovx 小鼠的 LPS 刺激的 COX-II 活性和 NF-κB 激活明显较低。此外，Fat-1 BM 细胞产生的 TRAP 破骨细胞样细胞的数量明显少于 WT BM 细胞。综上所述，我们使用 Fat-1 转基因小鼠模型提供了进一步的见解，以阐明 n-3 FA 防止 Ovx 小鼠 BMD 丢失的机制。
