The Journal of Bone and Joint Surgery (American). 2006;88:148-154.
doi:10.2106/JBJS.F.00534
© 2006 The Journal of Bone and Joint Surgery, Inc.
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Alcohol-Induced Adipogenesis in a Cloned Bone-Marrow Stem Cell

Quanjun Cui, MD, Yisheng Wang, MD, Khaled J. Saleh, MD, MSc, FRCSC, Gwo-Jaw Wang, MD and Gary Balian, PhD

Corresponding author:
Quanjun Cui, MD
Department of Orthopaedic Surgery, University of Virginia, School of Medicine, Box 800159, Charlottesville, VA 22908.
E-mail address: qc4q{at}hscmail.mcc.virginia.edu

NOTE: The authors wish to thank Dr. M. Daniel Lane (Johns Hopkins University, Baltimore, Maryland), who provided 422(aP2) cDNA (700 base pairs), and Dr. John Wozney (Genetics Institute, Cambridge, Massachusetts), who provided osteocalcin cDNA (500 base pairs).

The authors did not receive grants or outside funding in support of their research for or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: Alcohol has been shown to be associated with osteoporosis and osteonecrosis in patients and in animal models. Recent studies have demonstrated that alcohol contributes to abnormal lipid metabolism in the stromal cells of bone marrow, but the mechanisms have not been defined. The purpose of this study was to evaluate the effects of alcohol on the differentiation of a stem cell that was cloned from bone marrow.

Methods: D1 cells (cloned bone-marrow stem cells from a BALB/c mouse) were treated either with increasing concentrations of ethanol (0.09, 0.15, and 0.21 mol/L) or without alcohol to serve as controls. Morphologic features of the cells were monitored with use of a phase-contrast microscope. Alkaline phosphatase activity was determined with use of a colorimetric assay. The expression of genes that are indicators of adipogenesis [422(aP2), PPAR{gamma}] and osteogenesis (osteocalcin) was evaluated using Northern blot and reverse transcription-polymerase chain reaction assays.

Results: The cells treated with ethanol started to accumulate triglyceride vesicles at day seven. The number of adipocytes and the percentage of the area that contained the cells with fat vesicles increased significantly (p < 0.05), and the level of alkaline phosphatase activity diminished with longer durations of exposure to ethanol and with higher concentrations. Analysis of gene expression showed diminished expression of osteocalcin. This occurred without a significant increase in the expression of either the fat-cell-specific gene 422(aP2) or PPAR{gamma} in cells treated with ethanol, suggesting that adipogenesis may occur at a point downstream in the fatty-acid-metabolism pathway.

Conclusions: Alcohol treatment decreases osteogenesis while enhancing adipogenesis in a cloned bone-marrow stem cell, indicating that alcohol abuse may be one of the mechanisms leading to osteoporosis and osteonecrosis. This finding explains the clinical observation that there is increased adipogenesis in alcohol-induced osteoporosis and osteonecrosis.

Clinical Relevance: The inhibition of bone-marrow adipogenesis and the concomitant enhancement of osteogenesis may provide a novel approach to the prevention or treatment of osteonecrosis and osteoporosis.


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