Chronic ethanol exposure is associated with a local increase in TNF-α and decreased proliferation in the rat distraction gap

Daniel S. Perrien, Zhendong Liu, Elizabeth C. Wahl, Robert C. Bunn, Robert A. Skinner, James Aronson, John Fowlkes, Thomas M. Badger, Charles K. Lumpkin

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Chronic alcohol consumption is a risk factor for osteoporosis and inhibits osseous repair and regeneration. We investigated the hypothesis that chronic ethanol exposure induces the expression of TNF-α and/or IL-1β and inhibits proliferation during distraction osteogenesis (DO). Following six weeks of liquid diet infusion (±ethanol) and 14 days of DO, the expression of TNF-α and IL-1β in the distraction gap and contralateral femoral marrow of adult male rats was examined by immunohistochemistry and RT-PCR, respectively. In the bone marrow, the expression of both TNF-α and IL-1β mRNA was significantly increased by ethanol (p<0.04 for both). In the DO gap, ethanol exposure increased the expression of TNF-α in both the fibrous interzone and primary matrix front (PMF), while IL-1β expression was not significantly affected in either region. A negative correlation was found between the percentage of PCNA+ and TNF+ cells in the PMF (p<0.015, R2=0.655). Incubation of MC3T3-E1 cells with ethanol for 24 or 48 h produced a time and dose dependent two- to fourfold increase in TNF-α transcripts as measured by RT-PCR, demonstrating that ethanol can directly induce TNF-α expression in osteoblast-like cells. These results support the hypothesis that attenuation of bone formation by ethanol may be mediated, in part, by local increases in TNF-α during osteogenesis.

Original languageEnglish
Pages (from-to)179-189
Number of pages11
Issue number6
StatePublished - Sep 21 2003

Bibliographical note

Funding Information:
The authors respectfully thank the National Institutes of Health/NIAAA for their support of this work through grant AA12223 and Matthew Ferguson, Shanda Ferguson, Kim Hale, and Brit Young for their expert technical assistance.


  • Alcohol
  • Bone formation
  • Interleukin-1 beta
  • Osteoblast
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology


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