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.

驻留在组织中的巨噬细胞高度适应其组织特定的微环境，并被各种炎症信号激活，并受到遗传和环境因素的调控。破骨细胞和小胶质细胞是骨骼和大脑中巨噬细胞谱系的不同组织驻留细胞，分别负责骨质疏松症和阿尔茨海默氏病（AD）的病理变化。与一般人群的患病率相比，AD患者更容易观察到骨质疏松症。AD的诊断通常要等到潜在的病理生理变化进展并引起大脑结构和功能不可逆转的损害后才进行。因此，对高风险个体的早期诊断和干预对于修改临床过程必不可少。多效性是一种遗传变异影响多种性状的现象，而两个性状之间的遗传相关性可能暗示着一种共有的分子机制。在这篇综述中，我们讨论了破骨细胞和小胶质细胞分别在骨骼和大脑中的Pyk2介导​​的肌动蛋白聚合途径是骨质疏松症和AD共同危险因素的水平多效介质。