ArticleStem cell research & therapy2020
High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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93 citing papers in PubMed, 162 citations in OpenAlex.
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- Tendon stem/progenitor cells in heterotopic ossification: functional regulation, molecular mechanisms and targeted therapeutic strategies.Journal of orthopaedic translation · 2026Review
- Cell apoptosis in ischemic stroke: Focus on lipid metabolism.Neural regeneration research · 2026Article
- The role of the SIRT1/FOXO1 axis in regulating autophagy and inflammation in endometriosis.Journal of translational medicine · 2026Article
- Impact of preoperative blood lipid levels on early outcomes following arthroscopic rotator cuff repair: A retrospective analysis.Medicine · 2026Article
- Chronic Cholesterol Exposure Disrupts Macrophage Polarization and Cytokine Secretion in a 3D Microenvironment.ACS omega · 2026Article
- FOXO1 enhances G6PD expression to promote cancer cell antioxidative capacity.Journal of molecular cell biology · 2025Article
- Exosomal miR-212-5p promotes tendon repair via targeting FOXO1 to activate PP1A/YAP1 signaling.Communications biology · 2025Article
- Cholesterol metabolism on stem cell fate determination: a frontier horizon.Stem cell research & therapy · 2025Review
- Roles of lactylation in lipid metabolism and related diseases.Cell death discovery · 2025Review
- Tendon Aging: A Silent Enemy Revealed Strategies for Effective Treatment.Aging medicine (Milton (N.S.W)) · 2025Review
- Knockdown of the snoRNA-Jouvence Blocks the Proliferation and Leads to the Death of Human Primary Glioblastoma Cells.Non-coding RNA · 2025Article
- Life-threatening risk factors contribute to the development of diseases with the highest mortality through the induction of regulated necrotic cell death.Cell death & disease · 2025Review
- Association between neutrophil to high-density lipoprotein cholesterol ratio and hearing loss: a cross-sectional study from NHANES.Journal of health, population, and nutrition · 2025Article
- Reducing PKCδ inhibits tumor growth through growth hormone by inhibiting PKA/CREB/ERK signaling pathway in pituitary adenoma.Scientific reports · 2025Article
- Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring molecular and cellular signaling pathways: Unraveling the pathogenesis of tendinopathy.Journal of orthopaedic translation · 2025Review
- Ablation of Hepatic Asah1 Gene Disrupts Hepatic Lipid Homeostasis and Promotes Fibrotic Nonalcoholic Steatohepatitis in Mice.The American journal of pathology · 2025Article
33 more citing papers are in PubMed but not listed here.
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11 authors at 2 institutions in 1 country.
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Abstract
backgroundHypercholesterolemia increases the risk of tendon pain and tendon rupture. Tendon-derived stem cells (TDSCs) play a vital role in the development of tendinopathy. Our previous research found that high cholesterol inhibits tendon-related gene expression in TDSCs. Whether high cholesterol has other biological effects on TDSCs remains unknown.
methodsTDSCs isolated from female SD rats were exposed to 10 mg/dL cholesterol for 24 h. Then, cell apoptosis was assessed using flow cytometry and fluorescence microscope. RFP-GFP-LC3 adenovirus transfection was used for measuring autophagy. Signaling transduction was measured by immunofluorescence and immunoblotting. In addition, Achilles tendons from ApoE -/- mice fed with a high-fat diet were histologically assessed using HE staining and immunohistochemistry.
resultsIn this work, we verified that 10 mg/dL cholesterol suppressed cell proliferation and migration and induced G0/G1 phase arrest. Additionally, cholesterol induced apoptosis and autophagy simultaneously in TDSCs. Apoptosis induction was related to increased expression of cleaved caspase-3 and BAX and decreased expression of Bcl-xL. The occurrence of autophagic flux and accumulation of LC3-II demonstrated the induction of autophagy by cholesterol. Compared with the effects of cholesterol treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) enhanced apoptosis, while the apoptosis inhibitor Z-VAD-FMK diminished cholesterol-induced autophagy. Moreover, cholesterol triggered reactive oxygen species (ROS) generation and activated the AKT/FOXO1 pathway, while the ROS scavenger NAC blocked cholesterol-induced activation of the AKT/FOXO1 pathway. NAC and the FOXO1 inhibitor AS1842856 rescued the apoptosis and autophagy induced by cholesterol. Finally, high cholesterol elevated the expression of cleaved caspase-3, Bax, LC3-II, and FOXO1 in vivo.
conclusionThe present study indicated that high cholesterol induced apoptosis and autophagy through ROS-activated AKT/FOXO1 signaling in TDSCs, providing new insights into the mechanism of hypercholesterolemia-induced tendinopathy. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.
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