PMID- 17391719
OWN - NLM
STAT- MEDLINE
DCOM- 20070813
LR  - 20181227
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 220
IP  - 3
DP  - 2007 May 1
TI  - Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: role 
      of the TNF signaling axis.
PG  - 302-10
AB  - 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 microg/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.
FAU - Wahl, Elizabeth C
AU  - Wahl EC
AD  - Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research 
      Institute, Little Rock, AR 72202, USA.
FAU - Aronson, James
AU  - Aronson J
FAU - Liu, Lichu
AU  - Liu L
FAU - Liu, Zhendong
AU  - Liu Z
FAU - Perrien, Daniel S
AU  - Perrien DS
FAU - Skinner, Robert A
AU  - Skinner RA
FAU - Badger, Thomas M
AU  - Badger TM
FAU - Ronis, Martin J J
AU  - Ronis MJ
FAU - Lumpkin, Charles K Jr
AU  - Lumpkin CK Jr
LA  - eng
GR  - 1CORR16517-01/PHS HHS/United States
GR  - R01 AA012223-05A3/AA/NIAAA NIH HHS/United States
GR  - AA12223/AA/NIAAA NIH HHS/United States
GR  - R01 AA012223-06/AA/NIAAA NIH HHS/United States
GR  - R01 AA012223/AA/NIAAA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070224
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TNF Receptor-Associated Factor 1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3K9958V90M (Ethanol)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2E1)
SB  - IM
MH  - Animals
MH  - Bone Marrow/drug effects/metabolism
MH  - Central Nervous System Depressants/administration & dosage/pharmacology
MH  - Cytochrome P-450 CYP2E1/genetics/metabolism
MH  - Ethanol/administration & dosage/blood/*pharmacology
MH  - Interleukin-6/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Animal
MH  - Osteogenesis/drug effects/physiology
MH  - Osteogenesis, Distraction/*methods
MH  - Osteotomy/methods
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor/antagonists & inhibitors
MH  - Recombinant Proteins/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - *Signal Transduction
MH  - TNF Receptor-Associated Factor 1/metabolism/pharmacology
MH  - Tibia/surgery
MH  - Tumor Necrosis Factor-alpha/genetics/*pharmacology
PMC - PMC1892174
MID - NIHMS22951
EDAT- 2007/03/30 09:00
MHDA- 2007/08/19 09:00
PMCR- 2007/06/15
CRDT- 2007/03/30 09:00
PHST- 2006/12/05 00:00 [received]
PHST- 2007/01/24 00:00 [revised]
PHST- 2007/02/06 00:00 [accepted]
PHST- 2007/03/30 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/03/30 09:00 [entrez]
PHST- 2007/06/15 00:00 [pmc-release]
AID - S0041-008X(07)00073-7 [pii]
AID - 10.1016/j.taap.2007.02.011 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2007 May 1;220(3):302-10. doi: 
      10.1016/j.taap.2007.02.011. Epub 2007 Feb 24.