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Updated: Nov 18, 2025
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Two macrophages, osteoclasts and microglia: from development to pleiotropy
Ji-Won Lee1,2, In-Hee Lee3, Tadahiro Iimura2
1Department of Nephrology, Transplant Research Program, Boston Children's Hospital, Boston, MA, 02115, USA.
Abstract:
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.
Insights
Shared risk factors for osteoporosis and Alzheimer's disease (AD) may stem from the Pyk2-mediated actin polymerization pathway. This pathway in osteoclasts and microglia could offer new avenues for early diagnosis and intervention in AD and osteoporosis.
Area of Science:
- Immunology
- Neuroscience
- Bone Biology
Background:
- Tissue-resident macrophages, including osteoclasts (bone) and microglia (brain), are crucial in their respective microenvironments.
- Osteoporosis and Alzheimer's disease (AD) share higher prevalence in affected individuals, suggesting common underlying mechanisms.
- Current AD diagnosis often occurs after irreversible brain damage, highlighting the need for earlier detection and intervention strategies.
Purpose of the Study:
- To explore the molecular mechanisms linking osteoporosis and Alzheimer's disease (AD).
- To identify potential horizontal pleiotropic mediators responsible for shared risk factors between these conditions.
- To discuss the role of the Pyk2-mediated actin polymerization pathway in this context.
Main Methods:
- Review of existing literature on tissue-resident macrophages, osteoporosis, and AD.
- Analysis of genetic correlations and pleiotropy between traits.
- Focus on the Pyk2-mediated actin polymerization pathway in osteoclasts and microglia.
Main Results:
- Osteoclasts and microglia, macrophage lineage cells, are implicated in the pathology of osteoporosis and AD, respectively.
- The Pyk2-mediated actin polymerization pathway is proposed as a horizontal pleiotropic mediator.
- This pathway links shared risk factors contributing to both osteoporosis and AD.
Conclusions:
- The Pyk2-mediated actin polymerization pathway represents a shared molecular mechanism for osteoporosis and AD.
- Understanding this pathway could facilitate earlier diagnosis and intervention for individuals at risk.
- Targeting this pathway may offer therapeutic strategies for both conditions.
