Oxygen Sensing in Osteocytes: From Physiology to Age-related Osteoporosis.

IF 5.3 2区医学

Current Osteoporosis Reports Pub Date : 2025-06-21 DOI:10.1007/s11914-025-00920-7

Kathryn Janeczko, Rafiou Agoro

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引用次数: 0

Abstract

Purpose of the review: The purpose of this review article is to discuss how oxygen sensing mechanisms regulate the expression of key osteocyte markers such as podoplanin (E11), sclerostin (SOST), receptor activator of nuclear factor-κB ligand (RANKL), and fibroblast growth factor 23 (FGF23); summarize the relevance of targeting oxygen sensing pathways in osteocytes to improve bone health; and highlight the importance of osteocyte oxygen sensing mechanisms in maintaining good bone health during aging.

Recent findings: Oxygen sensing in osteocytes regulates osteocyte dendrites formation, bone mass and mineral metabolism through the regulation of E11, SOST, RANKL, and FGF23. Hypoxia Induced Factor (HIF) stabilization in osteocytes increases the activity of the histone deacetylase SIRT1 which represses SOST expression and increases the expression of FGF23. These recent findings suggest that targeting oxygen-associated pathways can be leveraged to control osteo-anabolic response and mineral metabolism. Aging is associated with the increase of circulating SOST; therefore, the mechanisms associated with SOST overproduction in bone may be linked to age-related changes in oxygen sensing in osteocytes. Understanding the changes of oxygen sensing mechanisms in osteocytes during aging may offer a therapeutic avenue to control SOST overproduction, a negative regulator of bone formation and therefore prevent age-related bone loss. We discuss how oxygen-sensing controls osteocyte physiology and how aging-mediated dysregulation of oxygen bioavailability promotes osteoporosis. We also explore how oxygen-modulating therapies can be used to improve bone healthspan.

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骨细胞中的氧感应：从生理学到年龄相关性骨质疏松症。

综述目的：本文旨在探讨氧敏感机制如何调节骨细胞关键标志物如足平面蛋白（E11）、硬化蛋白（SOST）、核因子-κB配体受体激活因子（RANKL）和成纤维细胞生长因子23 （FGF23）的表达；综述靶向骨细胞氧感应通路与改善骨健康的相关性并强调骨细胞氧感应机制在维持良好的骨骼健康老化过程中的重要性。近期研究发现：骨细胞中的氧感知通过调控E11、SOST、RANKL和FGF23来调节骨细胞树突形成、骨量和矿物质代谢。骨细胞中的缺氧诱导因子（HIF）稳定增加组蛋白去乙酰化酶SIRT1的活性，从而抑制SOST的表达并增加FGF23的表达。这些最近的发现表明，靶向氧相关途径可以用来控制骨合成代谢反应和矿物质代谢。衰老与循环SOST升高有关；因此，骨中SOST过量产生的相关机制可能与骨细胞中氧感知的年龄相关变化有关。了解骨细胞在衰老过程中氧传感机制的变化可能为控制SOST的过度产生提供治疗途径，SOST是骨形成的负调节因子，因此可以预防与年龄相关的骨质流失。我们讨论了氧感应如何控制骨细胞生理，以及衰老介导的氧生物利用度失调如何促进骨质疏松症。我们还探讨了如何使用氧调节疗法来改善骨骼健康。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Osteoporosis Reports ENDOCRINOLOGY & METABOLISM-

CiteScore

8.40

自引率

2.30%

发文量

期刊介绍： This journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of osteoporosis. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as current and future therapeutics, epidemiology and pathophysiology, and evaluation and management. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.