Lee Ji-Won, Lee In-Hee, Iimura Tadahiro, Kong Sek Won
Department of Nephrology, Transplant Research Program, Boston Children's Hospital, Boston, MA, 02115, USA.
Department of Pharmacology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.
Bone Res. 2021 Feb 10;9(1):11. doi: 10.1038/s41413-020-00134-w.
Tissue-resident macrophages are highly specialized to their tissue-specific microenvironments, activated by various inflammatory signals and modulated by genetic and environmental factors. Osteoclasts and microglia are distinct tissue-resident cells of the macrophage lineage in bone and brain that are responsible for pathological changes in osteoporosis and Alzheimer's disease (AD), respectively. Osteoporosis is more frequently observed in individuals with AD compared to the prevalence in general population. Diagnosis of AD is often delayed until underlying pathophysiological changes progress and cause irreversible damages in structure and function of brain. As such earlier diagnosis and intervention of individuals at higher risk would be indispensable to modify clinical courses. Pleiotropy is the phenomenon that a genetic variant affects multiple traits and the genetic correlation between two traits could suggest a shared molecular mechanism. In this review, we discuss that the Pyk2-mediated actin polymerization pathway in osteoclasts and microglia in bone and brain, respectively, is the horizontal pleiotropic mediator of shared risk factors for osteoporosis and AD.
组织驻留巨噬细胞高度特化于其组织特异性微环境，受各种炎症信号激活，并受遗传和环境因素调节。破骨细胞和小胶质细胞是巨噬细胞谱系在骨骼和大脑中不同的组织驻留细胞，分别负责骨质疏松症和阿尔茨海默病（AD）的病理变化。与普通人群相比，AD患者中更常观察到骨质疏松症。AD的诊断往往延迟到潜在的病理生理变化进展并导致大脑结构和功能的不可逆转损害时。因此，对高危个体进行早期诊断和干预对于改变临床病程至关重要。多效性是指一个基因变异影响多个性状，两个性状之间的遗传相关性可能暗示共享的分子机制。在本综述中，我们讨论了分别在骨骼和大脑中的破骨细胞和小胶质细胞中由Pyk2介导的肌动蛋白聚合途径是骨质疏松症和AD共享风险因素的水平多效性介质。
