Bioenergetic programs of cancellous and cortical bone are distinct and differ with age and mechanical loading.

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Carolyn Chlebek, Tyler J McNeill, Muyin Huang, Maia S Raynor, Marjolein C H van der Meulen
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Abstract

Mechanical loading induces bone formation in young rodents, but mechanoresponsiveness is reduced with age. Glycolytic activity and mitochondrial dysfunction increase with age and may change bone mechanotransduction. To evaluate load-induced changes to bioenergetic activity in young and adult animals, we loaded the tibia of 10-wk and 26-wk female C57BL/6J mice and examined transcriptomic responses at the mid-diaphysis, and metaphyseal cortical shell and cancellous core. Across all biological processes, oxidative phosphorylation and mitochondrial pathways were most often enriched with loading and had contrasting enrichment in young and adult animals. Following loading, young animals had temporally-coordinated differential expression of mitochondrial-associated genes, with greatest expression at the mid-diaphysis. In adults, bioenergetic gene expression was lower compared to young animals. To assess individual contributions of glycolysis and pyruvate-mediated oxidative phosphorylation to load-induced bone formation in vivo, we inhibited each pathway therapeutically and loaded the tibia of young and adult female mice for 2 weeks. In both young and adult mice, loading increased cortical bone mass, but inhibition of oxidative phosphorylation reduced cortical area and moment of inertia in both loaded and control limbs. Conversely, load-induced improvements of adult cancellous bone depended on glycolysis. In summary, mechanical loading transcriptionally activated mitochondrial pathways in an age-specific manner and bioenergetic inhibition revealed unique metabolic programs for cortical and cancellous bone.

松质骨和皮质骨的生物能量程序是不同的,随年龄和机械负荷而不同。
机械载荷诱导幼鼠骨形成,但机械反应性随年龄增长而降低。糖酵解活性和线粒体功能障碍随年龄增长而增加,并可能改变骨机械转导。为了评估负荷引起的幼龄和成年动物生物能量活性的变化,我们对10周龄和26周龄雌性C57BL/6J小鼠的胫骨进行了负荷,并检测了骨干中部、干骺端皮质壳和松质核心的转录组反应。在所有生物过程中,氧化磷酸化和线粒体途径最常随着负荷而富集,并且在幼龄和成年动物中富集程度不同。加载后,幼龄动物线粒体相关基因的时间协调差异表达,在中膈处表达最多。与幼龄动物相比,成年动物的生物能量基因表达较低。为了评估糖酵解和丙酮酸介导的氧化磷酸化对体内负荷诱导的骨形成的个体贡献,我们在治疗上抑制了每种途径,并对年轻和成年雌性小鼠的胫骨进行了2周的负荷。在年轻和成年小鼠中,负荷增加了皮质骨量,但氧化磷酸化抑制减少了负荷和对照肢的皮质面积和惯性矩。相反,负荷诱导的成人松质骨的改善依赖于糖酵解。总之,机械负荷以年龄特异性的方式激活线粒体通路,生物能量抑制揭示了皮质骨和松质骨独特的代谢程序。
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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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