Transient plasma membrane disruptions (PMD) occur in osteocytes with in vitro and in vivo loading, initiating mechanotransduction. The goal here was to determine whether osteocyte PMD formation or repair is affected by aging. Osteocytes from old (24 months) mice developed fewer PMD (−76% females, −54% males) from fluid shear than young (3 months) mice, and old mice developed fewer osteocyte PMD (−51%) during treadmill running. This was due at least in part to decreased pericellular matrix production, as studies revealed that pericellular matrix is integral to formation of osteocyte PMD, and aged osteocytes produced less pericellular matrix (−55%). Surprisingly, osteocyte PMD repair rate was faster (+25% females, +26% males) in osteocytes from old mice, and calcium wave propagation to adjacent nonwounded osteocytes was blunted, consistent with impaired mechanotransduction downstream of PMD in osteocytes with fast PMD repair in previous studies. Inducing PMD via fluid flow in young osteocytes in the presence of oxidative stress decreased postwounding cell survival and promoted accelerated PMD repair in surviving cells, suggesting selective loss of slower‐repairing osteocytes. Therefore, as oxidative stress increases during aging, slower‐repairing osteocytes may be unable to successfully repair PMD, leading to slower‐repairing osteocyte death in favor of faster‐repairing osteocyte survival. Since PMD are an important initiator of mechanotransduction, age‐related decreases in pericellular matrix and loss of slower‐repairing osteocytes may impair the ability of bone to properly respond to mechanical loading with bone formation. These data suggest that PMD formation and repair mechanisms represent new targets for improving bone mechanosensitivity with aging.

中文翻译：

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细胞周基质产生的减少和细胞膜修复增强的选择可能会削弱骨细胞对衰老骨骼中机械负荷的反应。

在体外和体内负荷下，骨细胞中会发生瞬时质膜破坏（PMD），从而引发机械转导。此处的目的是确定骨细胞PMD的形成或修复是否受到衰老的影响。年龄较大（24个月）小鼠的骨细胞通过液压剪切产生的PMD（雌性为-76％，雌性为-54％）要比幼年（3个月）的小鼠少，而老年小鼠在跑步机上的骨细胞PMD（-51％）较少。这至少部分是由于减少的细胞周基质产生，因为研究表明，细胞周基质是骨细胞PMD形成不可或缺的部分，而老化的骨细胞产生的细胞周基质较少（-55％）。令人惊讶的是，老小鼠的骨细胞中骨细胞的PMD修复速度更快（雌性+ 25％，雄性+ 26％），并且钙波传播到相邻未受伤的骨细胞的过程变钝了，与先前研究中具有快速PMD修复的骨细胞中PMD下游机械转导受损有关。在存在氧化应激的情况下，通过年轻骨细胞中的流体流动诱导PMD降低了伤口后细胞的存活率，并促进了存活细胞中PMD修复的加速，表明修复较慢的骨细胞选择性丢失。因此，随着衰老过程中氧化应激的增加，修复速度较慢的骨细胞可能无法成功修复PMD，从而导致修复速度较慢的骨细胞死亡，有利于修复速度更快的骨细胞存活。由于PMD是机械转导的重要引发剂，因此与年龄相关的细胞周围基质减少以及修复速度较慢的骨细胞的丢失可能会损害骨骼对骨骼形成的机械负荷做出适当反应的能力。