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Title: Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: Role of the TNF signaling axis

Abstract

Tumor necrosis factor-alpha (TNF-{alpha}) is an inflammatory cytokine that modulates osteoblastogenesis. In addition, the demonstrated inhibitory effects of chronic ethanol exposure on direct bone formation in rats are hypothetically mediated by TNF-{alpha} signaling. The effects in mice are unreported. Therefore, we hypothesized that in mice (1) administration of a soluble TNF receptor 1 derivative (sTNF-R1) would protect direct bone formation during chronic ethanol exposure, and (2) administration of recombinant mouse TNF-{alpha} (rmTNF-{alpha}) to ethanol naive mice would inhibit direct bone formation. We utilized a unique model of limb lengthening (distraction osteogenesis, DO) combined with liquid diets to measure chronic ethanol's effects on direct bone formation. Chronic ethanol exposure resulted in increased marrow TNF, IL-1, and CYP 2E1 RNA levels in ethanol-treated vs. control mice, while no significant weight differences were noted. Systemic administration of sTNF-R1 during DO (8.0 mg/kg/2 days) to chronic ethanol-exposed mice resulted in enhanced direct bone formation as measured radiologically and histologically. Systemic rmTNF-{alpha} (10 {mu}g/kg/day) administration decreased direct bone formation measures, while no significant weight differences were noted. We conclude that chronic ethanol-associated inhibition of direct bone formation is mediated to a significant extent by the TNF signaling axis in a mouse model.

Authors:
 [1];  [2];  [3];  [3];  [1];  [1];  [1];  [4];  [5];  [3];  [6];  [3];  [7]
  1. Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202 (United States)
  2. Department of Pediatrics, College of Medicine University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States)
  3. (United States)
  4. Department of Orthopaedics, College of Medicine University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States)
  5. Department of Physiology and Biophysics College of Medicine University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States)
  6. Department of Pharmacology and Toxicology, College of Medicine University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States)
  7. Department of Pediatrics, College of Medicine University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States) and Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202 (United States). E-mail: lumpkincharlesk@uams.edu
Publication Date:
OSTI Identifier:
20976922
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 220; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2007.02.011; PII: S0041-008X(07)00073-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ETHANOL; INFLAMMATION; LIMBS; MICE; RATS; RECEPTORS; RNA; SKELETON

Citation Formats

Wahl, Elizabeth C., Aronson, James, Department of Orthopaedics, College of Medicine University of Arkansas for Medical Sciences, Little Rock, AR 72202, Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, Liu, Lichu, Liu, Zhendong, Perrien, Daniel S., Skinner, Robert A., Badger, Thomas M., Arkansas Children's Nutrition Center, Little Rock, AR 72202, Ronis, Martin J.J., Arkansas Children's Nutrition Center, Little Rock, AR 72202, and Lumpkin, Charles K. Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: Role of the TNF signaling axis. United States: N. p., 2007. Web. doi:10.1016/j.taap.2007.02.011.
Wahl, Elizabeth C., Aronson, James, Department of Orthopaedics, College of Medicine University of Arkansas for Medical Sciences, Little Rock, AR 72202, Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, Liu, Lichu, Liu, Zhendong, Perrien, Daniel S., Skinner, Robert A., Badger, Thomas M., Arkansas Children's Nutrition Center, Little Rock, AR 72202, Ronis, Martin J.J., Arkansas Children's Nutrition Center, Little Rock, AR 72202, & Lumpkin, Charles K. Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: Role of the TNF signaling axis. United States. doi:10.1016/j.taap.2007.02.011.
Wahl, Elizabeth C., Aronson, James, Department of Orthopaedics, College of Medicine University of Arkansas for Medical Sciences, Little Rock, AR 72202, Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, Liu, Lichu, Liu, Zhendong, Perrien, Daniel S., Skinner, Robert A., Badger, Thomas M., Arkansas Children's Nutrition Center, Little Rock, AR 72202, Ronis, Martin J.J., Arkansas Children's Nutrition Center, Little Rock, AR 72202, and Lumpkin, Charles K. Tue . "Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: Role of the TNF signaling axis". United States. doi:10.1016/j.taap.2007.02.011.
@article{osti_20976922,
title = {Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: Role of the TNF signaling axis},
author = {Wahl, Elizabeth C. and Aronson, James and Department of Orthopaedics, College of Medicine University of Arkansas for Medical Sciences, Little Rock, AR 72202 and Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202 and Liu, Lichu and Liu, Zhendong and Perrien, Daniel S. and Skinner, Robert A. and Badger, Thomas M. and Arkansas Children's Nutrition Center, Little Rock, AR 72202 and Ronis, Martin J.J. and Arkansas Children's Nutrition Center, Little Rock, AR 72202 and Lumpkin, Charles K.},
abstractNote = {Tumor necrosis factor-alpha (TNF-{alpha}) is an inflammatory cytokine that modulates osteoblastogenesis. In addition, the demonstrated inhibitory effects of chronic ethanol exposure on direct bone formation in rats are hypothetically mediated by TNF-{alpha} signaling. The effects in mice are unreported. Therefore, we hypothesized that in mice (1) administration of a soluble TNF receptor 1 derivative (sTNF-R1) would protect direct bone formation during chronic ethanol exposure, and (2) administration of recombinant mouse TNF-{alpha} (rmTNF-{alpha}) to ethanol naive mice would inhibit direct bone formation. We utilized a unique model of limb lengthening (distraction osteogenesis, DO) combined with liquid diets to measure chronic ethanol's effects on direct bone formation. Chronic ethanol exposure resulted in increased marrow TNF, IL-1, and CYP 2E1 RNA levels in ethanol-treated vs. control mice, while no significant weight differences were noted. Systemic administration of sTNF-R1 during DO (8.0 mg/kg/2 days) to chronic ethanol-exposed mice resulted in enhanced direct bone formation as measured radiologically and histologically. Systemic rmTNF-{alpha} (10 {mu}g/kg/day) administration decreased direct bone formation measures, while no significant weight differences were noted. We conclude that chronic ethanol-associated inhibition of direct bone formation is mediated to a significant extent by the TNF signaling axis in a mouse model.},
doi = {10.1016/j.taap.2007.02.011},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 220,
place = {United States},
year = {Tue May 01 00:00:00 EDT 2007},
month = {Tue May 01 00:00:00 EDT 2007}
}