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Two macrophages, osteoclasts and microglia: from development to pleiotropy.

Ji-Won Lee^1,2, In-Hee Lee³, Tadahiro Iimura²

¹Department of Nephrology, Transplant Research Program, Boston Children's Hospital, Boston, MA, 02115, USA.

|February 11, 2021

Summary

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.

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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.