ArticleCell death discovery2025
MGP regulates the adipogenic differentiation of mesenchymal stem cells in osteoporosis via the Ca2+/CaMKII/RIP140/FABP3 axis.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Research Hotspots and Emerging Trends in Osteoporosis Epigenetics.Genetics research · 2026Article
- PBX1 promotes osteoporosis by upregulating HMGB1 to suppress osteogenic differentiation of bone marrow mesenchymal stem cells.Stem cell research & therapy · 2025Article
- Exploring the Shared Genetic Characteristics of Peri-Implantitis and Osteoporosis: A Transcriptomic Analysis Perspective.International dental journal · 2025Article
- [Preventive Regulation of Bone Marrow Mesenchymal Stem Cell Differentiation by α-Zearalenol Ameliorates Bone Loss in Osteoporotic Rats].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
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Authors and funding
15 authors.
Funding
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Abstract
The dysregulation of bone marrow mesenchymal stem cells (BM-MSCs) is crucial in the pathogenesis of osteoporosis, and adipogenic differentiation of BM-MSCs is considered an essential factor in this process. However, the mechanisms underlying the regulation of MSC adipogenic differentiation require further investigation. MGP (Matrix Gla Protein) was reported to impair the osteogenic differentiation. However, the mechanisms through which MGP regulates osteoporosis and bone-fat imbalance in MSCs are still unclear. In this study, we confirmed that the expression of MGP upregulated in osteoporosis and has a negative correlation with BMD (bone mineral density). Gain- and loss-of-function experiments were performed to ensure the role of MGP in MSC adipogenic differentiation. Mechanistically, MGP increased intracellular free Ca2+ levels and enhanced CaMKII phosphorylation, which in turn activated RIP140 protein degradation. This led to an increase in the transcription of FABP3, ultimately promoting adipogenic differentiation in MSCs. Furthermore, we demonstrated that using recombinant adeno-associated virus 9 (rAAV9) to silence MGP has the effect of alleviating bone loss and reversing the excessive bone marrow adipose tissue in mice with osteoporosis. In summary, our research has unveiled the regulatory role of MGP/Ca2+/CaMKII/RIP140/FABP3 axis in adipogenic differentiation in MSC and it might be a promising approach for osteoporosis treatment.
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