ArticleJournal of molecular medicine (Berlin, Germany)2023
LAMP2A regulates the balance of mesenchymal stem cell adipo-osteogenesis via the Wnt/β-catenin/GSK3β signaling pathway.
Article in Journal of molecular medicine (Berlin, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Chaperone-mediated autophagy in physiological homeostasis, disease and ageing.Nature reviews. Molecular cell biology · 2026Review
- FGFR1 frameshift mutation mediates the dysfunction of mesenchymal stem cells in craniofacial microsomia.Stem cell research & therapy · 2026Article
- Mechanisms of TRIM21-mediated RUNX2 degradation via chaperone-mediated autophagy in periodontitis.Cell biology and toxicology · 2026Article
- TRIM21 contributes to senile osteoporosis by shifting the osteoadipogenic balance toward adipogenesis in BMSCs.Science China. Life sciences · 2026Article
- Qi-Gui-Jian-Gu Decoction Accelerates Osteogenesis and Fracture Healing by Activating the Wnt/β-Catenin Signaling Pathway.Current computer-aided drug design · 2026Article
- Bidirectional regulation factor of bone marrow mesenchymal stromal cells differentiation: a focus on bone-fat balance in osteoporosis.Stem cell research & therapy · 2025Review
- Targeting chaperone-mediated autophagy to regulate osteoclast activity as a therapeutic strategy for osteoporosis.Materials today. Bio · 2025Article
- Heme oxygenase 1‑overexpressing bone marrow mesenchymal stem cell‑derived exosomes suppress interleukin‑1 beta‑induced apoptosis and aging of nucleus pulposus cells.Molecular medicine reports · 2025Article
- SLAMF8 regulates osteogenesis and adipogenesis of bone marrow mesenchymal stem cells via S100A6/Wnt/β-catenin signaling pathway.Stem cell research & therapy · 2024Article
- Article
- Loss of chaperone-mediated autophagy does not alter age-related bone loss in male mice.FASEB bioAdvances · 2024Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chaperone-mediated autophagy (CMA) plays multiple roles in cell metabolism. We found that lysosome-associated membrane protein type 2A (LAMP2A), a crucial protein of CMA, plays a key role in the control of mesenchymal stem cell (MSC) adipo-osteogenesis. We identified a differentially expressed CMA gene (LAMP2) in GEO datasets (GSE4911 and GSE494). Further, we performed co-expression analyses to define the relationships between CMA components genes and other relevant genes including Col1a1, Runx2, Wnt3 and Gsk3β. Mouse BMSCs (mMSCs) exhibiting Lamp2a gene knockdown (LA-KD) and overexpression (LA-OE) were created using an adenovirus system; then we investigated LAMP2A function in vitro by Western blot, Oil Red staining, ALP staining, ARS staining and Immunofluorescence analysis. Next, we used a modified mouse model of tibial fracture to investigate LAMP2A function in vivo. LAMP2A knockdown in mMSCs decreased the levels of osteogenic-specific proteins (COL1A1 and RUNX2) and increased those of the adipogenesis markers PPARγ and C/EBPα; LAMP2A overexpression had the opposite effects. The active-β-catenin and phospho-GSK3β (Ser9) levels were upregulated by LAMP2A overexpression and downregulated by LAMP2A knockdown. In the mouse model of tibial fracture, mMSC-overexpressing LAMP2A improved bone healing, as demonstrated by microcomputed tomography and histological analyses. In summary, LAMP2A positively regulates mMSC osteogenesis and suppresses adipo-osteogenesis, probably via Wnt/β-catenin/GSK3β signaling. LAMP2A promoted fracture-healing in the mouse model of tibial fracture. KEY MESSAGES: • LAMP2 positively regulates the mBMSCs osteogenic differentiation. • LAMP2 negatively regulates the mBMSCs adipogenic differentiation. • LAMP2 regulates mBMSCs osteogenesis via Wnt/β-catenin/GSK3β signaling pathway. • LAMP2 overexpression mBMSCs promote the fracture healing.
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