Chronic High Dose Alcohol Induces Osteopenia via Activation of mTOR Signaling in Bone Marrow Mesenchymal Stem Cells.

Abstract

Chronic consumption of excessive alcohol results in reduced bone mass, impaired bone structure, and increased risk of bone fracture. However, the mechanisms underlying alcohol-induced osteoporosis are not fully understood. Here, we show that high dose chronic alcohol consumption reduces osteogenic differentiation and enhances adipogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), leading to osteopenia in a mouse model. Mechanistically, impaired osteo/adipogenic lineage differentiation of BMMSCs is due to activation of a phosphatidylinositide 3-kinase/AKT/mammalian target of rapamycin (mTOR) signaling cascade, resulting in downregulation of runt-related transcription factor 2 and upregulation of peroxisome proliferator-activated receptor gamma via activation of p70 ribosomal protein S6 kinase. Blockage of the mTOR pathway by rapamycin treatment ameliorates alcohol-induced osteopenia by rescuing impaired osteo/adipogenic lineage differentiation of BMMSCs. In this study, we identify a previously unknown mechanism by which alcohol impairs BMMSC lineage differentiation and reveal a potential rapamycin-based drug therapy for alcohol-induced osteoporosis. Stem Cells 2016;34:2157-2168.

• Authors: Yao Liu, Xiaoxing Kou, Chider Chen, Wenjing Yu, Yingying Su, Yong Kim, Songtao Shi, Yi Liu
• Journal: Stem cells (Dayton, Ohio) (Stem Cells) Vol. 34 Issue 8 Pg. 2157-68 (08 2016) ISSN: 1549-4918 [Electronic] England
• PMID: 27145264 (Publication Type: Journal Article)
• Copyright: © 2016 AlphaMed Press.

Chemical References

• Ethanol
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Adipogenesis (drug effects)
• Animals
• Bone Diseases, Metabolic (etiology, metabolism)
• Bone Marrow Cells (drug effects, pathology)
• Cell Lineage (drug effects)
• Ethanol (adverse effects)
• Female
• Mesenchymal Stem Cells (drug effects, metabolism, pathology)
• Mice, Nude
• Phenotype
• Signal Transduction (drug effects)
• Sirolimus (pharmacology)
• TOR Serine-Threonine Kinases (metabolism)