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 ...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.展开更多
基金supported by the grants from the National Institution of Health(R01MH107205,R24OD024622,and U01TR002623)supported by Grantin-Aids for Scientific Research from the Japan Society for the Promotion of Science(19K10044).
文摘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.
