Yılmaz Dilara, Marques Francisco C, Gregorio Lorena, Schlatter Jérôme, Gehre Christian, Pararajasingam Thurgadevi, Qiu Wanwan, Mathavan Neashan, Qin Xiao-Hua, Wehrle Esther, Kuhn Gisela A, Müller Ralph
Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
AO Research Institute Davos, Davos Platz, Switzerland.
Bone Res. 2025 May 23;13(1):55. doi: 10.1038/s41413-025-00428-x.
Age-related osteoporosis poses a significant challenge in musculoskeletal health; a condition characterized by reduced bone density and increased fracture susceptibility in older individuals necessitates a better understanding of underlying molecular and cellular mechanisms. Emerging evidence suggests that osteocytes are the pivotal orchestrators of bone remodeling and represent novel therapeutic targets for age-related bone loss. Our study uses the prematurely aged Polg (PolgA) mouse model to scrutinize age- and sex-related alterations in musculoskeletal health parameters (frailty, grip strength, gait data), bone and particularly the osteocyte lacuno-canalicular network (LCN). Moreover, a new quantitative in silico image analysis pipeline is used to evaluate the alterations in the osteocyte network with aging. Our findings underscore the pronounced degenerative changes in the musculoskeletal health parameters, bone, and osteocyte LCN in PolgA mice as early as 40 weeks, with more prominent alterations evident in aged males. Our findings suggest that the PolgA mouse model serves as a valuable model for studying the cellular mechanisms underlying age-related bone loss, given the comparable aging signs and age-related degeneration of the bone and the osteocyte network observed in naturally aging mice and elderly humans.
与年龄相关的骨质疏松症对肌肉骨骼健康构成了重大挑战；这种疾病的特征是老年人骨密度降低和骨折易感性增加，因此有必要更好地了解其潜在的分子和细胞机制。新出现的证据表明，骨细胞是骨重塑的关键协调者，也是与年龄相关的骨质流失的新型治疗靶点。我们的研究使用早衰的Polg（PolgA）小鼠模型，来仔细研究肌肉骨骼健康参数（虚弱程度、握力、步态数据）、骨骼尤其是骨细胞腔隙-小管网络（LCN）中与年龄和性别相关的变化。此外，我们使用一种新的定量计算机图像分析流程来评估随着衰老骨细胞网络的变化。我们的研究结果强调，早在40周龄时，PolgA小鼠的肌肉骨骼健康参数、骨骼和骨细胞LCN就出现了明显的退行性变化，老年雄性小鼠的变化更为显著。我们的研究结果表明，鉴于在自然衰老的小鼠和老年人中观察到的类似衰老迹象以及骨骼和骨细胞网络的年龄相关退化，PolgA小鼠模型是研究与年龄相关骨质流失潜在细胞机制的有价值模型。
