Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Food Funct. 2020 Feb 26;11(2):1498-1512. doi: 10.1039/c9fo01944h.
Our previous work demonstrated that yak bone collagen peptides (YBP) possessed excellent osteogenic activity in vitro. However, associations between YBP and osteoporosis were less established, and the positive effect and underlying mechanism of YBP in the treatment of osteoporotic rats in vivo remained unclear. Herein, ovariectomized rats were intragastrically administered with YBP or 17β-estradiol for 12 weeks. Bone turnover markers, bone biomechanical parameters and bone microarchitecture were investigated to identify the specific changes of potential antagonistic effects of YBP on ovariectomized rats. Then, serum samples were analyzed by UPLC/Q-TOF-MS to identify metabolites. The results showed that YBP treatment remarkably altered the content of serum bone turnover markers and prevented the ovariectomy-induced deterioration of bone mechanical and microarchitecture characteristics. A total of forty-one biomarkers for which levels changed markedly upon treatment have been identified based on non-targeted metabolomics. Among them, twenty-one metabolites displayed a downward expression level, while twenty metabolites showed an upward expression level in the YBP group and finally were selected as potential biomarkers. The levels of these biomarkers displayed significant alterations and a tendency to be restored to normal values in YBP treated osteoporotic rats. A systematic network analysis of their corresponding pathways delineated that the protective or recovery effect of YBP on osteoporosis occurred primarily by regulating the amino acid metabolism and lipid metabolism (especially unsaturated fatty acid). Collectively, these findings highlight that such peptides hold promise in further advancement as a natural alternative for functional and health-promoting foods, which could be potentially used in mediated treatment of osteoporosis.
我们之前的工作表明，牦牛骨胶原蛋白肽（YBP）具有优异的体外成骨活性。然而，YBP 与骨质疏松症之间的关联尚未得到充分证实，其在体内治疗骨质疏松症大鼠中的积极作用和潜在机制尚不清楚。在此，通过灌胃给予去卵巢大鼠 YBP 或 17β-雌二醇 12 周。研究了骨转换标志物、骨生物力学参数和骨微观结构，以确定 YBP 对去卵巢大鼠潜在拮抗作用的具体变化。然后，通过 UPLC/Q-TOF-MS 分析血清样品以鉴定代谢物。结果表明，YBP 处理可显著改变血清骨转换标志物的含量，并防止去卵巢引起的骨机械和微观结构特征恶化。基于非靶向代谢组学共鉴定出 41 种代谢物，其水平因治疗而明显改变。其中，21 种代谢物的表达水平下降，而 YBP 组中有 20 种代谢物的表达水平上升，最终被选为潜在的生物标志物。这些生物标志物的水平在骨质疏松症大鼠中发生了显著变化，并呈现出恢复正常的趋势。对其相应途径的系统网络分析表明，YBP 对骨质疏松症的保护或恢复作用主要通过调节氨基酸代谢和脂质代谢（特别是不饱和脂肪酸）来发挥。总之，这些发现表明，这些肽作为功能性和促进健康食品的天然替代品具有进一步发展的潜力，可用于骨质疏松症的治疗。
