title: Chronic ethanol exposure is associated with a local increase in TNF-alpha and decreased proliferation in the rat distraction gap.
abstract: 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.
authors.affiliation: Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, AR, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Perrien
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Liu
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wahl
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bunn
authors.forename: Robert A
authors.initials: RA
authors.lastname: Skinner
authors.forename: James
authors.initials: J
authors.lastname: Aronson
authors.forename: John
authors.initials: J
authors.lastname: Fowlkes
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.forename: Charles K
authors.initials: CK
authors.lastname: Lumpkin
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology*; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D019857:Osteogenesis, Distraction; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol