Site-specific CGRP innervation coincides with bone formation during fracture healing and modeling:: A study in rat angulated tibia

Site-specific CGRP innervation coincides with bone formation during fracture healing and modeling:: A study in rat angulated tibia
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DOI:
10.1002/jor.20406
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发表时间:
2007-09-01
影响因子:
2.8
通讯作者:
Ahmed, Mahmood
Ahmed, Mahmood
中科院分区:
医学3区
文献类型:
--
作者:
Li, Jian;Kreicbergs, Andris;Ahmed, Mahmood

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感觉神经肽参与局部骨转换是已知的,但知之甚少。在本研究中,我们分析了74只大鼠胫骨直骨折和角骨折愈合和建模过程中神经元CGRP的发生情况。骨折后1-12周,采用x线摄影和半定量免疫组织化学方法评估骨折部位的骨愈合和建模情况。含CGRP的再生神经纤维在骨折愈伤组织和软骨细胞附近被观察到,在第1周,两处骨折已经出现编织骨。值得注意的是,在骨折后3至5周,它主要位于成角骨折的凹侧,以发芽入骨的方式出现。在这两例骨折中,骨折骨痂在骨折后第3周达到最高值。在成角骨折中,从第3周到第12周,凸侧骨痂厚度减少了11%,凹侧骨痂厚度增加了365%。第3周观察到,与完整骨相比,直骨折的总神经元CGRP增加27倍,角骨折的总神经元CGRP增加38倍。在两种类型骨折中,神经元CGRP在凹侧大于凸侧;这种差异在成角骨折中更为明显。CGRP免疫反应性与新骨形成量明显一致,尤其是在成角骨折的凹侧。综合结果表明,骨折引起了含有CGRP的新神经纤维的强烈、局部生长,这可能是骨折愈合和建模的先决条件。(c) 2007年骨科研究学会。
Sensory neuropeptide involved in local bone turnover is known, but poorly understood. In the present study, we analyze the occurrence of neuronal CGRP during healing and modeling of straight and angular tibial fractures in 74 rats. Bone healing and modeling was assessed by radiography and reirmervation by semi-quantitative immunohistochemistry method at fracture site between 1-12 weeks postfracture. The regenerating nerve fibers containing CGRP were observed in fracture callus as well as in close proximity to chondrocytes, with woven bone in both fractures already at week 1. Notably, it located predominantly on the concave side of angulated fracture in the manner of sprouting into bone from weeks 3 to 5 postfracture. In both fractures, fracture calluses peaked radiographically at week 3 postfracture. In angulated fracture, a reduction of 11% in callus thickness on convex side and an increase of 365% on concave side were noted from weeks 3 to 12. A 27-fold increase in total neuronal CGRP in straight fracture and 38-fold increases in angular fracture compared to intact bone was observed at week 3. In both types of fracture, neuronal CGRP was greater on the concave side than the convex; this difference was more pronounced in the angulated fracture. CGRP immunoreactivity clearly coincides with amount of new bone formation especially on the concave side of angulated fracture. The combined results suggest that fracture evokes an intense, localized in-growth of new nerve fibers containing CGRP, which may prove to be a prerequisite of fracture healing and modeling. (c) 2007 Orthopaedic Research Society.