Metabolic shifts in ratio of ucOcn to cOcn towards bone resorption contribute to age-dependent bone loss in male mice.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Matthew Bernhard, Obinna Okorie, Wei-Ju Tseng, Mengcun Chen, Julia Danon, Mingshu Cui, Elisabeth Lashbrooks, Yanmei Yang, Bin Wang
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Abstract

The study of the senile osteoporosis in men still lags significantly behind in women. The changes of protein molecule levels and their relationships with bone loss remain poorly understood. In the present study, we used C57BL/6J male mice at ages from 3 to 24 months to delineate the mechanisms of aging effects on bone loss. We employed the micro-computed tomography, mechanical testing, histomorphometry assays, and detection of serum levels of undercarboxylated osteocalcin (ucOcn) and carboxylated osteocalcin (cOcn) to assess bone mass changes and their relationships with ratios of ucOcn to cOcn in mice from different age groups. The results showed that mouse trabecular bone mass reduced gradually with age while cortical bone loss and mechanical property changes mostly occurred in advanced age. Our findings further demonstrated that the increase in osteoclast activity and the decrease in osteoblast function were significantly corelated with blood levels of ucOcn and cOcn, respectively. The dynamic metabolic changes of ucOcn to cOcn ratio were correlated with age-dependent bone loss in mice. In summary, metabolic shifts in ratio of ucOcn to cOcn towards bone resorption from young adult to elderly mice contribute to the pathogenesis of age-related bone loss. Simultaneously monitoring blood ratios of ucOcn to cOcn may be useful to predict the status of bone mass in vivo.

在雄性小鼠体内,ucOcn 和 cOcn 的比例发生了新陈代谢变化,转向骨吸收,导致了年龄依赖性骨质流失。
对男性老年性骨质疏松症的研究仍明显落后于女性。蛋白质分子水平的变化及其与骨质流失的关系仍然鲜为人知。在本研究中,我们利用 3 至 24 个月大的 C57BL/6J 雄性小鼠来阐明衰老对骨质流失的影响机制。我们采用显微计算机断层扫描、机械测试、组织形态测定法以及检测血清中羧基化骨钙素(ucOcn)和羧基化骨钙素(cOcn)的水平来评估不同年龄组小鼠的骨量变化及其与ucOcn和cOcn比率的关系。结果表明,小鼠骨小梁的骨量随着年龄的增长而逐渐减少,而皮质骨的损失和机械性能的变化则主要发生在高龄阶段。我们的研究结果进一步表明,破骨细胞活性的增加和成骨细胞功能的降低分别与血液中 ucOcn 和 cOcn 的水平显著相关。ucOcn 与 cOcn 比率的动态代谢变化与小鼠年龄依赖性骨质流失相关。总之,从幼年小鼠到老年小鼠,ucOcn 和 cOcn 的代谢比例向骨吸收方向转变,是与年龄相关的骨质流失的发病机制之一。同时监测血液中ucOcn和cOcn的比例可能有助于预测体内骨量的状况。
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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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