Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response.
Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response.
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DOI：
10.15252/emmm.201404487
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发表时间：
2015-05
影响因子：
11.1
通讯作者：
Nanchahal J
中科院分区：
文献类型：
--
作者：
Chan JK;Glass GE;Ersek A;Freidin A;Williams GA;Gowers K;Espirito Santo AI;Jeffery R;Otto WR;Poulsom R;Feldmann M;Rankin SM;Horwood NJ;Nanchahal J
创伤引发愈合的机制尚不清楚。对这些事件的精确理解可以确定加速愈合的干预措施，并可转化为临床领域。我们之前报道了在骨折部位添加低剂量重组人TNF （rhTNF）增强小鼠胫骨骨折模型的骨折修复。在这里，我们发现局部rhTNF治疗仅在损伤后24小时内有效，此时中性粒细胞是主要的炎症细胞浸润。全身给药抗tnf损伤骨折愈合。rhTNF的加入增强了中性粒细胞的募集，并通过CCL2的产生促进了单核细胞的募集。相反，中性粒细胞的消耗或趋化因子受体CCR2的抑制导致骨折愈合明显受损。脆性或骨质疏松性骨折是一个主要的医学问题，因为它们与永久性残疾和过早死亡有关。使用小鼠脆性骨折模型，我们发现局部rhTNF治疗可改善骨折修复早期的愈合。如果转化为临床，这种促进骨折愈合的方法将降低与延迟患者活动相关的发病率和死亡率。
The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24 h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization.
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影响因子：
6.3
作者：
Donaldson, L. J.;Reckless, I. P.;Shelton, N. J.
通讯作者：
Shelton, N. J.
影响因子：
4.4
作者：
Brodmerkel, CM;Huber, R;Vaddi, K
通讯作者：
Vaddi, K
DOI：
10.1073/pnas.87.13.5134
发表时间：
1990-07-01
影响因子：
11.1
作者：
CUSHING, SD;BERLINER, JA;FOGELMAN, AM
通讯作者：
FOGELMAN, AM
影响因子：
4.4
作者：
Bennouna, S;Bliss, SK;Denkers, EY
通讯作者：
Denkers, EY
影响因子：
6.2
作者：
Alexander, Kylie A.;Chang, Ming K.;Pettit, Allison R.
通讯作者：
Pettit, Allison R.