FoxO3 Regulates Mouse Bone Mesenchymal Stem Cell Fate and Bone-Fat Balance During Skeletal Aging
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View abstract on PubMed
Summary
This summary is machine-generated.Forkhead box O 3 (FoxO3) controls bone cell differentiation. Restoring FoxO3 levels in aged mice combats osteoporosis and excess marrow fat by balancing bone formation and fat accumulation.
Area Of Science
- Cell Biology
- Gerontology
- Orthopedics
Background
- Age-related osteoporosis involves imbalanced differentiation of bone mesenchymal stem cells (BMSCs).
- Forkhead box O 3 (FoxO3) influences lifespan and cell differentiation.
- The role of FoxO3 in age-related bone loss and marrow fat accumulation requires investigation.
Purpose Of The Study
- To investigate the role of FoxO3 in regulating age-related bone loss and marrow fat accumulation.
- To determine if FoxO3 modulates osteogenic and adipogenic differentiation in BMSCs.
Main Methods
- Detected FoxO3 expression in BMSCs from young and aged mice (in vivo and in vitro).
- Modulated FoxO3 expression using adenoviral vectors.
- Evaluated bone-fat balance via alizarin red S staining, oil red O staining, qPCR, Western blot, and histology.
Main Results
- FoxO3 expression was downregulated in aged BMSCs, correlating with bone loss and fat accumulation.
- Overexpression of FoxO3 in aged mice alleviated bone loss and reduced marrow fat.
- FoxO3 suppressed adipogenesis and promoted osteogenesis by downregulating PPAR-γ and Notch signaling.
Conclusions
- FoxO3 is crucial for maintaining the bone-fat balance in BMSCs.
- FoxO3 downregulation contributes to age-related osteoporosis and marrow fat accumulation.
- FoxO3 represents a potential therapeutic target for preventing age-related osteoporosis.
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