Li Jian, Kreicbergs Andris, Bergström Jonas, Stark Andreas, Ahmed Mahmood
Section of Orthopaedics, Institution of Molecular Medicine and Surgery, Research Center M3:02, Karolinska University Hospital, SE 171 76, Stockholm, Sweden.
J Orthop Res. 2007 Sep;25(9):1204-12. doi: 10.1002/jor.20406.
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 reinnervation 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.
参与局部骨转换的感觉神经肽已为人所知，但了解甚少。在本研究中，我们分析了74只大鼠胫骨直形骨折和角形骨折愈合及塑形过程中神经元降钙素基因相关肽（CGRP）的出现情况。通过X线摄影评估骨折愈合和塑形情况，并在骨折后1至12周采用半定量免疫组织化学方法评估骨折部位的神经再支配情况。在骨折痂以及靠近软骨细胞处观察到含有CGRP的再生神经纤维，在骨折后第1周时两种骨折的编织骨中均已出现。值得注意的是，从骨折后第3至5周，它主要位于角形骨折的凹侧，以向骨内芽生的方式存在。在两种骨折中，骨折痂在X线片上均在骨折后第3周达到峰值。在角形骨折中，从第3至12周，凸侧痂厚度减少了11%，凹侧增加了365%。在第3周时，与完整骨相比，直形骨折中神经元CGRP总量增加了27倍，角形骨折增加了38倍。在两种类型的骨折中，凹侧的神经元CGRP均多于凸侧；这种差异在角形骨折中更为明显。CGRP免疫反应性与新骨形成量明显一致，尤其是在角形骨折的凹侧。综合结果表明，骨折引发了含有CGRP的新神经纤维的强烈局部向内生长，这可能是骨折愈合和塑形的一个先决条件。
