Apoptotic vesicles rectify senile bone-fat imbalance by activating Thy1-ERK-TAZ axis.
Yuhe Jiang1, Jianqi She2,3, Zeying Wang1
1Department of Prosthodontics, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, Peking University School and Hospital of Stomatology, NMPA Key Laboratory for Dental Materials, Beijing, 100081, China.
Journal of Nanobiotechnology
|December 13, 2025
Summary
Aging alters mesenchymal stem cell (MSC)-derived apoptotic vesicles (apoVs), impacting bone-fat balance. Engineered apoVs enriched with Thy1 restore bone health and improve metabolism in aged models.
Area of Science:
- Biomedical Science
- Regenerative Medicine
- Aging Research
Background:
- Senile bone-fat imbalance is a major health issue in aging populations.
- Mesenchymal stem cell (MSC)-derived apoptotic vesicles (apoVs) play a role in this imbalance.
- Aging affects the composition and function of apoVs.
Purpose of the Study:
- Investigate age-related changes in MSC-derived apoV heterogeneity.
- Develop a therapeutic strategy for age-related bone-fat metabolic disorders.
- Identify key molecular mechanisms involved in apoV function.
Main Methods:
- Protein cargo analysis of MSC-derived apoVs from aged donors.
- Functional validation of Thy1's role in osteogenesis and adipogenesis.
- Engineering Thy1-enriched apoVs using magnetic-activated sorting and protein corona technology.
- In vivo studies in aged mouse models.
Main Results:
- MSC-derived apoVs show age-dependent compositional changes, with declining Thy1 levels.
- Thy1 is crucial for apoV-mediated osteoinduction and anti-adipogenesis.
- Engineered Thy1-enriched apoVs enhanced osteogenesis and suppressed adipogenesis via the Thy1-ERK-TAZ pathway.
- Treatment with engineered apoVs improved bone mass, reduced marrow fat, and corrected lipid metabolism in aged mice.
Conclusions:
- Thy1 serves as a functional biomarker for aging-related apoV heterogeneity.
- Engineered Thy1-enriched apoVs offer a scalable therapeutic approach for senile bone-fat imbalance.
- The Thy1-ERK-TAZ pathway provides a target for extracellular vesicle-based interventions against age-related diseases.
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