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衰老会降低雌性C57BL/6小鼠的骨细胞陷窝-小管周转率。

Aging decreases osteocyte lacunar-canalicular turnover in female C57BL/6 mice.

作者信息

Vahidi Ghazal, Boone John Connor, Hoffman Fawn, Heveran Chelsea M

出版信息

bioRxiv. 2023 Dec 16:2023.12.15.571934. doi: 10.1101/2023.12.15.571934.

Abstract

Osteocytes engage in bone resorption and mineralization surrounding their expansive lacunar-canalicular system (LCS) through LCS turnover. However, fundamental questions persist about where, when, and how often osteocytes engage in LCS turnover and how these processes change with aging. Furthermore, whether LCS turnover depends on tissue strain remains unexplored. To address these questions, we utilized confocal scanning microscopy, immunohistochemistry, and scanning electron microscopy to characterize osteocyte LCS turnover in the cortical (mid-diaphysis) and cancellous (metaphysis) femurs from young (5 mo) and early-old-age (22 mo) female C57BL/6JN mice. LCS bone mineralization was measured by the presence of perilacunar fluorochrome labels. LCS bone resorption was measured by immunohistochemical markers of bone resorption. The dynamics of LCS turnover were estimated from serial fluorochrome labeling, where each mouse was administered two labels between 2 days and 16 days before euthanasia. Osteocyte participation in mineralizing their surroundings is highly abundant in both cortical and cancellous bone of young adult mice but significantly decreases with aging. LCS bone resorption also decreases with aging. Aging has a greater impact on LCS turnover dynamics in cancellous bone than in cortical bone. Lacunae with recent LCS turnover have larger lacunae in both age groups. The impacts of aging on LCS turnover also varies with cortical region of interest and intracortical location, suggesting a dependence on tissue strain. The impact of aging on decreasing LCS turnover may have significant implications for bone quality and mechanosensation.

摘要

骨细胞通过骨陷窝-小管系统(LCS)更新参与其周围骨吸收和矿化过程。然而,关于骨细胞在何处、何时以及多久进行一次LCS更新,以及这些过程如何随衰老而变化等基本问题依然存在。此外,LCS更新是否依赖于组织应变尚不清楚。为了解决这些问题,我们利用共聚焦扫描显微镜、免疫组织化学和扫描电子显微镜对年轻(5个月)和老年早期(22个月)雌性C57BL/6JN小鼠股骨皮质(骨干中段)和松质骨(干骺端)中的骨细胞LCS更新进行了表征。通过骨陷窝周围荧光染料标记的存在来测量LCS骨矿化。通过骨吸收的免疫组织化学标记物来测量LCS骨吸收。LCS更新的动力学通过连续荧光染料标记进行估计,在安乐死之前的2天至16天之间给每只小鼠注射两种标记物。在年轻成年小鼠的皮质骨和松质骨中,骨细胞参与其周围矿化的情况都非常丰富,但随着衰老显著减少。LCS骨吸收也随着衰老而减少。衰老对松质骨中LCS更新动力学的影响比对皮质骨的影响更大。在两个年龄组中,近期有LCS更新的骨陷窝都更大。衰老对LCS更新的影响也因感兴趣的皮质区域和皮质内位置而异,这表明其依赖于组织应变。衰老对LCS更新减少的影响可能对骨质量和机械感觉有重大影响。

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