The Diminishing Returns of Mechanical Loading and Potential Mechanisms that Desensitize Osteocytes.
The Diminishing Returns of Mechanical Loading and Potential Mechanisms that Desensitize Osteocytes.
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DOI：
10.1007/s11914-021-00693-9
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发表时间：
2021-08
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
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作者：
适应机械负荷对于维持骨量至关重要，并为预防与年龄相关的骨质流失和骨质疏松症提供治疗潜力。然而，随着合成代谢反应迅速饱和，增加负荷持续时间会遇到“回报递减”的情况。因此，对日常活动和重复负荷的合成代谢反应受到潜在机制的限制，这些机制使骨骼在细胞水平上脱敏并失去反应。骨细胞是对骨骼负荷做出反应并促进整体合成代谢反应的主要细胞。尽管许多骨细胞响应负载而激活的信号机制本质上被认为是合成代谢的，但其中一些也会使骨细胞对进一步的刺激不敏感，从而形成限制骨细胞整体反应的负反馈循环。本次综述的目的是检查可能导致机械敏感性丧失的潜在机制。特别是，我们检查了离子通道和信号分子的失活/脱敏以及内吞作用和细胞骨架重组的潜在作用。定义负反馈环的重要性在于有可能识别出使骨细胞保持敏感性的独特目标。通过这样做，我们可以开始培育新的策略，利用日常活动的合成代谢性质，这些活动会反复加载骨骼。
Adaptation to mechanical loading is critical to maintaining bone mass and offers therapeutic potential to preventing age-related bone loss and osteoporosis. However, increasing the duration of loading is met with “diminishing returns” as the anabolic response quickly becomes saturated. As a result, the anabolic response to daily activities and repetitive bouts of loading is limited by the underlying mechanisms that desensitize and render bone unresponsive at the cellular level. Osteocytes are the primary cells that respond to skeletal loading and facilitate the overall anabolic response. Although many of osteocytes’ signaling mechanisms activated in response to loading are considered anabolic in nature, several of them can also render osteocytes insensitive to further stimuli and thereby creating a negative feedback loop that limits osteocytes’ overall response. The purpose of this review is to examine the potential mechanisms that may contribute to the loss of mechanosensitivity. In particular, we examined the inactivation/desensitization of ion channels and signaling molecules along with the potential role of endocytosis and cytoskeletal reorganization. The significance in defining the negative feedback loop is the potential to identify unique targets for enabling osteocytes to maintain their sensitivity. In doing so, we can begin to cultivate new strategies that capitalize on the anabolic nature of daily activities that repeatedly load the skeleton.
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通讯作者：
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通讯作者：
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