ArticleAlcoholism, clinical and experimental research2020
Ethanol Inhibits Mesenchymal Stem Cell Osteochondral Lineage Differentiation Due in Part to an Activation of Forkhead Box Protein O-Specific Signaling.
Article in Alcoholism, clinical and experimental research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 15 citations in OpenAlex.
- Mechanical loading primes MSC-derived exosomes to promote cartilage repair.Bioactive materials · 2026Article
- Aging Exacerbates Binge Ethanol-Mediated Bone Toxicity in Mice.Alcohol, clinical & experimental research · 2026Article
- Review
- Acetate derived from metabolism of ethanol affects gene expression in bone and contributes to delays in chondrogenic differentiation.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- New developments on the effects of alcohol use on immunity, inflammation and organ function: A summary of the 2024 Alcohol and Immunology Research Interest Group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2025Article
- The Roles of Forkhead Box O3a (FOXO3a) in Bone and Cartilage Diseases - A Narrative Review.Drug design, development and therapy · 2025Review
- Vitamin E Improves Cellular and Structural Bone Histomorphometry in an Alcohol-Induced Osteoporosis Rat Model.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Forkhead box O proteins: steering the course of stem cell fate.Cell regeneration (London, England) · 2024Review
- 'Triple clear': a systematic and comprehensive surgical process for Campanacci grades II and III giant cell tumors of the bone, with or without pathological fracture and slight joint invasion.World journal of surgical oncology · 2023Article
- New insights into the mechanism of alcohol-mediated organ damage via its impact on immunity, metabolism, and repair pathways: A summary of the 2021 Alcohol and Immunology Research Interest Group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2022Review
- Episodic alcohol exposure attenuates mesenchymal stem cell chondrogenic differentiation during bone fracture callus formation.Alcoholism, clinical and experimental research · 2022Article
- Management of the Cavity After Removal of Giant Cell Tumor of the Bone.Frontiers in surgery · 2021Review
- Impact of Alcohol on Bone Health, Homeostasis and Fracture repair.Current pathobiology reports · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
backgroundDuring bone fracture repair, resident mesenchymal stem cells (MSCs) differentiate into chondrocytes, to form a cartilaginous fracture callus, and osteoblasts, to ossify the collagen matrix. Our laboratory previously reported that alcohol administration led to decreased cartilage formation within the fracture callus of rodents and this effect was mitigated by postfracture antioxidant treatment. Forkhead box protein O (FoxO) transcription factors are activated in response to intracellular reactive oxygen species (ROS), and alcohol has been shown to increase ROS. Activation of FoxOs has also been shown to inhibit canonical Wnt signaling, a necessary pathway for MSC differentiation. These findings have led to our hypothesis that alcohol exposure decreases osteochondrogenic differentiation of MSCs through the activation of FoxOs.
methodsPrimary rat MSCs were treated with ethanol (EtOH) and assayed for FoxO expression, FoxO activation, and downstream target expression. Next, MSCs were differentiated toward osteogenic or chondrogenic lineages in the presence of 50 mM EtOH and alterations in osteochondral lineage marker expression were determined. Lastly, osteochondral differentiation experiments were repeated with FoxO1/3 knockdown or with FoxO1/3 inhibitor AS1842856 and osteochondral lineage marker expression was determined.
resultsEtOH increased the expression of FoxO3a at mRNA and protein levels in primary cultured MSCs. This was accompanied by an increase in FoxO1 nuclear localization, FoxO1 activation, and downstream catalase expression. Moreover, EtOH exposure decreased expression of osteogenic and chondrogenic lineage markers. FoxO1/3 knockdown restored proosteogenic and prochondrogenic lineage marker expression in the presence of 50 mM EtOH. However, FoxO1/3 inhibitor only restored proosteogenic lineage marker expression.
conclusionsThese data show that EtOH has the ability to inhibit MSC differentiation, and this ability may rely, at least partially, on the activation of FoxO transcription factors.
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