Document Detail

Inhibitory effect of alcohol on osteogenic differentiation in human bone marrow-derived mesenchymal stem cells.
MedLine Citation:
PMID:  15084905     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Alcohol-induced osteoporosis is characterized by a considerable suppression of osteogenesis. The objective of this investigation was to determine the effect of alcohol on gene expression, protein synthesis, and mineralization in human bone marrow-derived mesenchymal stem cells induced toward osteogenic differentiation in vitro. METHODS: Human bone marrow-derived mesenchymal stem cells induced toward osteogenesis were cultured in the presence or absence of 50 mM alcohol. Stem cells were characterized by using SH2 antibody to the cell-surface antigen CD105/endoglin, and their proliferation in the presence of alcohol was quantified. The expression of genes for early, middle, and late markers of the osteogenic lineage was quantified by Northern analysis, and bone matrix protein synthesis was assayed. The effect of alcohol on cell-mediated matrix mineralization in terminally differentiated cultures was determined by von Kossa staining. RESULTS: Fluorescence-activated cell sorting analysis of human mesenchymal stem cells separated with a Percoll gradient proved 99% homogeneity by using SH2 antibody to the surface antigen CD105. Dose-dependent inhibition of proliferation of these stem cells occurred at concentrations greater than 50 mM alcohol. Gene expression of osteoblast-specific factor 2/core binding factor a1 (Osf2/Cbfa1), type I collagen, alkaline phosphatase, and osteocalcin (early, middle, and late markers for osteogenesis, respectively) was analyzed with and without osteogenic induction and treatment with 50 mM alcohol. After induction, Osf2/Cbfa1 levels were unresponsive to alcohol. To determine the effect of alcohol on human mesenchymal stem cell progression along the osteogenic pathway, messenger RNA (mRNA) levels for type I collagen, alkaline phosphatase, and osteocalcin were examined after osteogenic induction. After osteogenic induction, alcohol down-regulated the gene expression of type I collagen and significantly reduced its synthesis. Alcohol did not alter mRNA expression of alkaline phosphatase, a midstage marker for osteogenesis, but significantly decreased its activity compared with osteogenic induction alone. After induction, osteocalcin remained unchanged by alcohol at both the mRNA and protein levels. Histochemistry revealed decreased alkaline phosphatase staining and fewer alkaline phosphatase-positive cells in alcohol-treated human mesenchymal stem cell cultures. von Kossa staining revealed a reduction in the number of mineralizing nodules in stem cell cultures after alcohol treatment. CONCLUSIONS: Collectively, the data suggest that alcohol alters osteogenic differentiation in human bone marrow-derived mesenchymal stem cell cultures during lineage progression and provide further insight into alcohol-induced reduced bone formation.
Zhaodi Gong; Frederick H Wezeman
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Alcoholism, clinical and experimental research     Volume:  28     ISSN:  0145-6008     ISO Abbreviation:  Alcohol. Clin. Exp. Res.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-04-15     Completed Date:  2004-05-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7707242     Medline TA:  Alcohol Clin Exp Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  468-79     Citation Subset:  IM    
Department of Orthopaedic Surgery and Rehabilitation and the Alcohol Research Program, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, USA.
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MeSH Terms
Analysis of Variance
Bone Marrow Cells / cytology,  drug effects*,  metabolism
Cell Differentiation / drug effects*,  physiology
Dose-Response Relationship, Drug
Ethanol / pharmacology*
Mesenchymal Stem Cells / cytology,  drug effects*,  metabolism
Middle Aged
Osteogenesis / drug effects*,  physiology
Grant Support
Reg. No./Substance:

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