Inhibitory Effect of Alcohol on Osteogenic Differentiation in Human Bone Marrow–Derived Mesenchymal Stem Cells

摘要: : Background: Alcohol-induced osteoporosis is characterized by a considerable suppression of osteogenesis. The objective this investigation was to determine the effect alcohol on gene expression, protein synthesis, and mineralization in human bone marrow–derived mesenchymal stem cells induced toward osteogenic differentiation vitro. Methods: Human osteogenesis were cultured presence or absence 50 mM alcohol. Stem using SH2 antibody cell-surface antigen CD105/endoglin, their proliferation quantified. expression genes for early, middle, late markers lineage quantified Northern analysis, matrix synthesis assayed. cell-mediated terminally differentiated cultures determined von Kossa staining. Results: Fluorescence-activated cell sorting analysis separated with Percoll gradient proved 99% homogeneity surface CD105. Dose-dependent inhibition these occurred at concentrations greater than Gene osteoblast-specific factor 2/core binding a1 (Osf2/Cbfa1), type I collagen, alkaline phosphatase, osteocalcin (early, osteogenesis, respectively) analyzed without induction treatment After induction, Osf2/Cbfa1 levels unresponsive To progression along pathway, messenger RNA (mRNA) examined after induction. down-regulated collagen significantly reduced its synthesis. Alcohol did not alter mRNA midstage marker but decreased activity compared alone. remained unchanged both levels. Histochemistry revealed phosphatase staining fewer phosphatase–positive alcohol-treated cultures. reduction number mineralizing nodules treatment. Conclusions: Collectively, data suggest that alters during provide further insight into alcohol-induced formation.