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
Lumpkin CK Jr
中科院分区:
医学2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

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牵张成骨(DO)是一种通过机械牵张直接诱导新骨形成的过程。肿瘤坏死因子-α(TNF)是一种能够调节成骨细胞生成的细胞因子。假设TNF对啮齿类动物直接骨形成的直接作用是通过TNF受体1和/或2(TNFR 1/2)信号转导介导的。我们利用独特的小鼠DO模型来评估1)TNFR纯合无效基因改变对直接骨形成的影响和2)rmTNF对野生型(WT)、TNFR 1-/-(R1 KO)和TNR 2-/-(R2 KO)小鼠的影响。牵引间隙中直接骨形成的放射学和组织学分析表明,WT、R1 KO、R2 KO或TNFR 1-/- & R2 -/-(R1&2KO)小鼠之间没有显著差异。R1和2KO小鼠的血清TNF水平升高,但没有表现出对新骨形成的抑制。在DO期间通过渗透泵全身给予rmTNF(10 μ g/ kg/天)导致WT和R2 KO小鼠中间隙骨形成测量的显著抑制,但在R1 KO小鼠中没有。我们的结论是,外源性rmTNF和/或内源性TNF的作用,以抑制新骨形成在DO信号主要通过TNFR 1。
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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