骨重建
骨质疏松症
毛螺菌科
一氧化氮
骨吸收
化学
精氨酸
肠道菌群
瓜氨酸
破骨细胞
代谢性骨病
内科学
生物
细胞生物学
生物化学
医学
内分泌学
氨基酸
16S核糖体RNA
体外
基因
厚壁菌
作者
Dan Wang,Jing Cai,Qilin Pei,Zedong Yan,Feng Zhu,Zhe Zhao,R. Y. Liu,Xiangyang Guo,Tao Sun,Juan Liu,Yulan Tian,H. Q. Liu,Xi Shao,Jinghui Huang,Xiaoxia Hao,Qi Chang,Zhuojing Luo,Da Jing
出处
期刊:Cell Metabolism
[Elsevier]
日期:2024-06-01
卷期号:36 (6): 1252-1268.e8
被引量:1
标识
DOI:10.1016/j.cmet.2024.04.004
摘要
Although mechanical loading is essential for maintaining bone health and combating osteoporosis, its practical application is limited to a large extent by the high variability in bone mechanoresponsiveness. Here, we found that gut microbial depletion promoted a significant reduction in skeletal adaptation to mechanical loading. Among experimental mice, we observed differences between those with high and low responses to exercise with respect to the gut microbial composition, in which the differential abundance of Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial production of L-citrulline and its conversion into L-arginine were identified as key regulators of bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsiveness in normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancement of bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calcium positive feedback loop in osteocytes. This study identifies a promising anti-osteoporotic strategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metabolite axis.
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