Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia.
Int J Environ Res Public Health. 2019 Sep 9;16(18):3313. doi: 10.3390/ijerph16183313.
A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.
先前的动物研究表明，代谢综合征（MetS）与骨质疏松症之间存在正相关关系。传统上，MetS 调节骨重塑过程的机制集中在成熟成骨细胞和破骨细胞之间的相互作用，而骨细胞的作用尚未得到探索。我们之前的研究使用 MetS 诱导的骨质疏松症大鼠模型证明了生育三烯酚的促骨作用。本研究旨在探讨 MetS 诱导骨质疏松症大鼠骨中骨细胞衍生肽的表达，并用生育三烯酚治疗。将年龄匹配的雄性 Wistar 大鼠（12 周龄；n=42）分为七组实验。两组分别作为基线和正常组。其余五组给予高碳水化合物高脂肪（HCHF）饮食以诱导 MetS。从第 8 周开始，五组 HCHF 动物分别用生育酚耗尽玉米油（载体）、安纳托生育三烯酚（60 和 100mg/kg）和棕榈生育三烯酚（60 和 100mg/kg）治疗。研究结束时，处死大鼠并采集其右侧胫骨。从右侧胫骨近端干骺端提取蛋白质，测定骨肽水平，包括护骨素（OPG）、核因子-kappa B 受体激活剂可溶性配体（sRANKL）、骨硬化蛋白（SOST）、Dickkopf 相关蛋白 1（DKK-1）、成纤维细胞生长因子 23（FGF-23）和甲状旁腺激素（PTH）。与正常动物相比，载体处理的动物 sRANKL、SOST、DKK-1、FGF-23 和 PTH 水平更高。安纳托和棕榈生育三烯酚（60 和 100mg/kg）口服补充降低了 HCHF 动物的 sRANKL 和 FGF-23 水平。只有 100mg/kg 的安纳托和棕榈生育三烯酚降低了 HCHF 动物的 SOST 和 DKK-1 水平。总之，生育三烯酚通过调节骨细胞衍生的骨相关肽水平发挥潜在的促骨作用。
