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

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-alpha and/or IL-1beta and inhibits proliferation during distraction osteogenesis (DO). Following six weeks of liquid diet infusion (+/-ethanol) and 14 days of DO, the expression of TNF-alpha and IL-1beta 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-alpha and IL-1beta mRNA was significantly increased by ethanol (p<0.04 for both). In the DO gap, ethanol exposure increased the expression of TNF-alpha in both the fibrous interzone and primary matrix front (PMF), while IL-1beta 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, R(2)=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-alpha transcripts as measured by RT-PCR, demonstrating that ethanol can directly induce TNF-alpha 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-alpha during osteogenesis.