PMID- 27145264
OWN - NLM
STAT- MEDLINE
DCOM- 20171212
LR  - 20211204
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 34
IP  - 8
DP  - 2016 Aug
TI  - Chronic High Dose Alcohol Induces Osteopenia via Activation of mTOR Signaling in 
      Bone Marrow Mesenchymal Stem Cells.
PG  - 2157-68
LID - 10.1002/stem.2392 [doi]
AB  - 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.
CI  - (c) 2016 AlphaMed Press.
FAU - Liu, Yao
AU  - Liu Y
AD  - Department of Pediatric Dentistry, School of Stomatology, China Medical 
      University, Shenyang, China.
AD  - Liaoning Province Key Laboratory of Oral Disease, Shenyang, China.
AD  - Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University 
      of Southern California, Los Angeles, California, USA.
FAU - Kou, Xiaoxing
AU  - Kou X
AD  - Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University 
      of Southern California, Los Angeles, California, USA.
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania, School of 
      Dental Medicine, Philadelphia, Pennsylvania, USA.
FAU - Chen, Chider
AU  - Chen C
AD  - Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University 
      of Southern California, Los Angeles, California, USA.
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania, School of 
      Dental Medicine, Philadelphia, Pennsylvania, USA.
FAU - Yu, Wenjing
AU  - Yu W
AD  - Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University 
      of Southern California, Los Angeles, California, USA.
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania, School of 
      Dental Medicine, Philadelphia, Pennsylvania, USA.
FAU - Su, Yingying
AU  - Su Y
AD  - Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, 
      Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital 
      Medical University School of Stomatology, Beijing, China.
FAU - Kim, Yong
AU  - Kim Y
AD  - UCLA School of Dentistry, Los Angeles, California, USA.
FAU - Shi, Songtao
AU  - Shi S
AD  - Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University 
      of Southern California, Los Angeles, California, USA.
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania, School of 
      Dental Medicine, Philadelphia, Pennsylvania, USA.
FAU - Liu, Yi
AU  - Liu Y
AD  - Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, 
      Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital 
      Medical University School of Stomatology, Beijing, China.
LA  - eng
GR  - R01 AA021301/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20160530
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 3K9958V90M (Ethanol)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adipogenesis/drug effects
MH  - Animals
MH  - Bone Diseases, Metabolic/*etiology/*metabolism
MH  - Bone Marrow Cells/drug effects/*pathology
MH  - Cell Lineage/drug effects
MH  - Ethanol/*adverse effects
MH  - Female
MH  - Mesenchymal Stem Cells/drug effects/metabolism/*pathology
MH  - Mice, Nude
MH  - Phenotype
MH  - *Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Adipogenesis
OT  - Alcohol consumption
OT  - Bone marrow mesenchymal stem cells
OT  - Osteogenesis
OT  - Osteoporosis
OT  - Rapamycin
EDAT- 2016/05/05 06:00
MHDA- 2017/12/13 06:00
CRDT- 2016/05/05 06:00
PHST- 2015/12/15 00:00 [received]
PHST- 2016/03/14 00:00 [revised]
PHST- 2016/04/14 00:00 [accepted]
PHST- 2016/05/05 06:00 [entrez]
PHST- 2016/05/05 06:00 [pubmed]
PHST- 2017/12/13 06:00 [medline]
AID - 10.1002/stem.2392 [doi]
PST - ppublish
SO  - Stem Cells. 2016 Aug;34(8):2157-68. doi: 10.1002/stem.2392. Epub 2016 May 30.