Distraction osteogenesis in TNF receptor 1 deficient mice is protected from chronic ethanol exposure.

Distraction osteogenesis in TNF receptor 1 deficient mice is protected from chronic ethanol exposure.
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DOI:
10.1016/j.alcohol.2011.08.007
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发表时间:
2012-03
期刊:
Alcohol (Fayetteville, N.Y.)
影响因子:
--
通讯作者:
Lumpkin CK Jr
Lumpkin CK Jr
中科院分区:
其他
文献类型:
--
作者:
Wahl EC;Aronson J;Liu L;Skinner RA;Ronis MJ;Lumpkin CK Jr

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牵张成骨(DO)是一种骨科方案,其由于机械牵张的刺激作用而诱导直接新骨形成。已证明慢性乙醇(EtOH)暴露可抑制DO啮齿动物模型中的骨形成。此外,已证明1)肿瘤坏死因子-α(TNF)阻断剂对EtOH暴露具有保护作用,2)重组小鼠TNF(rmTNF)通过TNF受体1(TNFR 1)抑制EtOH未处理小鼠的直接骨形成。这些结果表明,抑制作用显着介导的TNF信号。因此,我们假设TNFR 1敲除(KO)小鼠的直接新骨形成将受到保护,免受EtOH暴露。我们利用了一种独特的小鼠DO模型与液体/食物饮食相结合,以比较EtOH对TNFR 1敲除(TNFR 1 KO)小鼠品系及其C57 BL/6(B6)对照品系小鼠的影响。在B6研究中,与之前的工作一致,牵引间隙中直接骨形成的放射学和组织学分析表明,与普通饲料或成对喂养的小鼠相比,EtOH具有显著的骨抑制作用。在TNFR 1 KO研究中,为了支持这一假设,牵引间隙骨形成的放射学和组织学分析均表明EtOH、食物喂养或成对喂养之间无显著差异。我们得出结论,外源性rmTNF和乙醇诱导的内源性TNF的行为,以抑制新骨形成DO信号主要通过TNFR 1。
Distraction Osteogenesis (DO) is an orthopedic protocol which induces direct new bone formation as a result of the stimulating effects of mechanical distraction. Chronic ethanol (EtOH) exposure has been demonstrated to inhibit bone formation in rodent models of DO. Further it has been demonstrated that 1) Tumor Necrosis Factor-α (TNF) blockers are protective against EtOH exposure and 2) recombinant mouse TNF (rmTNF) inhibits direct bone formation in EtOH naïve mice through TNF receptor 1 (TNFR1). These results suggest that the inhibitory effects are significantly mediated by TNF signaling. Therefore, we hypothesized that direct new bone formation in TNFR1 knockout (KO) mice would be protected from EtOH exposure. We utilized a unique model of mouse DO combined with liquid/chow diets to compare the effects of EtOH on both a strain of TNFR1 knockout (TNFR1KO) mice and on mice of their C57BL/6 (B6) control strain. In the B6 study, and in concordance with previous work, both radiological and histological analyses of direct bone formation in the distraction gaps demonstrated significant osteoinhibition due to EtOH compared to chow or pair-fed mice. In the TNFR1KO study and in support of the hypothesis, both radiological and histological analyses of distraction gap bone formation demonstrated no significant differences between the EtOH, chow fed, or pair-fed. We conclude that exogenous rmTNF and EtOH-induced endogenous TNF act to inhibit new bone formation during DO by signaling primarily through TNFR1.
DOI: 10.1016/j.alcohol.2006.08.004
发表时间: 2006-07-01
期刊: ALCOHOL
影响因子: 2.3
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发表时间: 2010-01
期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子: --
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