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Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
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Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging
Chang-Jun Li1,2, Ye Xiao1, Mi Yang1,2,3
1Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, China.
The Journal of Clinical Investigation
|October 24, 2018
Summary
A novel long noncoding RNA, Bmncr, controls bone marrow mesenchymal stem cell (BMSC) fate during aging. Restoring Bmncr levels reverses age-related bone loss and adiposity by promoting osteogenesis and inhibiting adipogenesis.
Area of Science:
- Stem cell biology
- Molecular biology
- Aging research
Background:
- Mesenchymal stem cells (MSCs) undergo age-related lineage shifts, impacting bone health.
- This switch contributes to bone loss and increased adiposity with age.
Purpose of the Study:
- To identify key regulators of age-related MSC fate.
- To elucidate the role of long noncoding RNAs in maintaining the osteogenic niche.
Main Methods:
- Generation of Bmncr-knockout (Bmncr-KO) and Bmncr-transgenic (Bmncr-Tg) mice.
- Analysis of bone mass, marrow adiposity, and gene expression.
- Investigated Bmncr's role in chromatin structure and protein interactions (TAZ, ABL, RUNX2, PPARG).
- Utilized adeno-associated viral vectors for gene manipulation in vivo and in human BMSCs.
Main Results:
- Bmncr depletion exacerbates age-related bone loss and adiposity.
- Bmncr overexpression in mice mitigates these age-related changes.
- Bmncr maintains the osteogenic niche by regulating fibromodulin (FMOD) and the BMP2 pathway.
- Bmncr facilitates TAZ complex formation, promoting osteogenesis and inhibiting adipogenesis.
- Restoring BMNCR in human BMSCs reversed age-related differentiation bias.
Conclusions:
- Bmncr is a critical regulator of the age-related osteogenic niche.
- BMNCR controls the cell fate switch in bone marrow mesenchymal stem cells.
- Targeting Bmncr offers a potential therapeutic strategy for age-related bone diseases.
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