Direct bone formation during distraction osteogenesis does not require TNFalpha receptors and elevated serum TNFalpha fails to inhibit bone formation in TNFR1 deficient mice.
Direct bone formation during distraction osteogenesis does not require TNFalpha receptors and elevated serum TNFalpha fails to inhibit bone formation in TNFR1 deficient mice.
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DOI:
10.1016/j.bone.2009.09.011
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发表时间:
2010-02
期刊:
影响因子:
4.1
通讯作者:
Lumpkin CK Jr
中科院分区:
文献类型:
--
作者:
Wahl EC;Aronson J;Liu L;Skinner RA;Miller MJ;Cockrell GE;Fowlkes JL;Thrailkill KM;Bunn RC;Ronis MJ;Lumpkin CK Jr
Distraction Osteogenesis (DO) is a process which induces direct new bone formation as a result of mechanical distraction. Tumor necrosis factor-α (TNF) is a cytokine that can modulate osteoblastogenesis. The direct effects of TNF on direct bone formation in rodents are hypothetically mediated through TNF receptor 1 and/or 2 (TNFR1/2) signaling. We utilized a unique model of mouse DO to assess the effects of 1) TNFR homozygous null gene alterations on direct bone formation and 2) rmTNF on wild type (WT), TNFR1 -/- (R1KO), and TNR2 -/- (R2KO) mice. Radiological and histological analyses of direct bone formation in the distraction gaps demonstrated no significant differences between the WT, R1KO, R2KO, or TNFR1 -/- & R2 -/- (R1&2KO) mice. R1&2KO mice had elevated levels of serum TNF but demonstrated no inhibition of new bone formation. Systemic administration by osmotic pump of rmTNF during DO (10 ug/ kg/day) resulted in significant inhibition of gap bone formation measures in WT and R2KO mice, but not in R1KO mice. We conclude that exogenous rmTNF and/or endogenous TNF act to inhibit new bone formation during DO by signaling primarily through TNFR1.
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