雌激素和雌激素受体介导骨病和修复的机械生物学。

IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Bone Pub Date : 2024-08-05 DOI:10.1016/j.bone.2024.117220
Vivian Shi, Elise F. Morgan
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引用次数: 0

摘要

众所周知,骨骼形成和吸收的平衡取决于机械和生化因素。除了细胞分泌的细胞因子和生长因子外,雌激素等性激素对维持骨骼健康也至关重要。尽管雌激素和雌激素受体(ERs)的直接骨保护功能已被广泛报道,但最近出现的证据表明,雌激素信号传导还在介导机械负荷对骨量维持和骨损伤愈合的影响方面发挥作用。最近的研究强调了雌激素和雌激素受体在骨机械感觉和机械传导的许多途径中的作用。研究表明,雌激素和雌激素可增强基于整合素的机械传导,以及典型的 Wnt/b-catenin、RhoA/ROCK 和 YAP/TAZ 通路。雌激素和ERs不仅影响成骨细胞的机械敏感性,还影响成骨细胞、破骨细胞和骨髓基质细胞的机械敏感性。本综述将强调雌激素和雌激素在骨力学生物学基础细胞机制中的这些作用,并讨论它们对骨质疏松症和骨折治疗的影响。更深入地了解雌激素与机械负荷之间的相互作用机制可能对解决当前激素和药物疗法的不足之处至关重要。包括高强度运动疗法在内的综合疗法可减轻不良副作用,为高危人群预防、治疗和管理骨质疏松提供长期有效的解决方案。此外,还将讨论新的局部荷尔蒙疗法机制对骨质疏松症治疗的未来影响,以及性荷尔蒙疗法在骨病之外的应用对骨骼健康的影响。
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Estrogen and estrogen receptors mediate the mechanobiology of bone disease and repair

It is well understood that the balance of bone formation and resorption is dependent on both mechanical and biochemical factors. In addition to cell-secreted cytokines and growth factors, sex hormones like estrogen are critical to maintaining bone health. Although the direct osteoprotective function of estrogen and estrogen receptors (ERs) has been reported extensively, evidence that estrogen signaling also has a role in mediating the effects of mechanical loading on maintenance of bone mass and healing of bone injuries has more recently emerged. Recent studies have underscored the role of estrogen and ERs in many pathways of bone mechanosensation and mechanotransduction. Estrogen and ERs have been shown to augment integrin-based mechanotransduction as well as canonical Wnt/b-catenin, RhoA/ROCK, and YAP/TAZ pathways. Estrogen and ERs also influence the mechanosensitivity of not only osteocytes but also osteoblasts, osteoclasts, and marrow stromal cells. The current review will highlight these roles of estrogen and ERs in cellular mechanisms underlying bone mechanobiology and discuss their implications for management of osteoporosis and bone fractures. A greater understanding of the mechanisms behind interactions between estrogen and mechanical loading may be crucial to addressing the shortcomings of current hormonal and pharmaceutical therapies. A combined therapy approach including high-impact exercise therapy may mitigate adverse side effects and allow an effective long-term solution for the prevention, treatment, and management of bone fragility in at-risk populations. Furthermore, future implications to novel local delivery mechanisms of hormonal therapy for osteoporosis treatment, as well as the effects on bone health of applications of sex hormone therapy outside of bone disease, will be discussed.

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来源期刊
Bone
Bone 医学-内分泌学与代谢
CiteScore
8.90
自引率
4.90%
发文量
264
审稿时长
30 days
期刊介绍: BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.
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