Arasapam G, Scherer M, Cool J C, Foster B K, Xian C J
Department of Physiology, University of Adelaide, Adelaide, South Australia, Australia.
J Cell Biochem. 2006 Oct 1;99(2):450-61. doi: 10.1002/jcb.20905.
Growth plate injuries often lead to bone growth defects, which primarily occur due to bony repair at injury sites. Bony repair is preceded by an injury-induced inflammatory response, which could play a role in regulating the repair process. Here, roles of two inflammatory mediators, cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), in the injury responses were analysed by examining their gene expression and effects of blocking their activities, respectively, with celecoxib and aminoguanidine during 2 days prior to and until 7 days after injury in a rat tibial growth plate injury model. Quantitative RT-PCR assays revealed upregulated expression of COX-2 on days 1 and 4 and iNOS on day 1. Histological analysis of injury sites revealed significant reductions in inflammatory infiltrate (particularly neutrophils) on day 1 in treated groups compared to saline control. While bony tissue proportions at injury sites were unaffected by either treatment, mesenchymal tissue proportions were larger but cartilaginous tissue proportions were smaller on day 8 (though statistically insignificant), and bone remodelling appeared delayed with a smaller bone marrow proportion on day 14 in both treatment groups. These findings suggest that COX-2 and iNOS mediate injury-induced inflammatory response, and may play a role in enhancing mesenchymal cell differentiation to cartilaginous cells and in promoting bone remodelling during bony repair of growth plate injury sites. Furthermore, increased expression of cartilage-related (collagen-2, collagen-10, SOX-9) and bone-related molecules (osteocalcin, cbfalpha-1) suggest involvement of both endochondral and direct bone formation mechanisms during bony repair.
生长板损伤常导致骨生长缺陷，这主要是由于损伤部位的骨修复所致。骨修复之前会出现损伤诱导的炎症反应，该反应可能在调节修复过程中发挥作用。在此，通过在大鼠胫骨生长板损伤模型中，分别在损伤前2天直至损伤后7天，用塞来昔布和氨基胍检测两种炎症介质环氧化酶2（COX - 2）和诱导型一氧化氮合酶（iNOS）的基因表达以及阻断其活性的效果，分析了它们在损伤反应中的作用。定量逆转录聚合酶链反应（RT - PCR）分析显示，COX - 2在第1天和第4天表达上调，iNOS在第1天表达上调。损伤部位的组织学分析显示，与生理盐水对照组相比，治疗组在第1天炎症浸润（尤其是中性粒细胞）显著减少。虽然损伤部位的骨组织比例不受任何一种治疗的影响，但在第8天，间充质组织比例较大而软骨组织比例较小（尽管无统计学意义），并且在第14天，两个治疗组的骨髓比例较小，骨重塑似乎延迟。这些发现表明，COX - 2和iNOS介导损伤诱导的炎症反应，并且可能在生长板损伤部位的骨修复过程中，在增强间充质细胞向软骨细胞分化以及促进骨重塑方面发挥作用。此外，软骨相关分子（胶原蛋白 - 2、胶原蛋白 - 10、SOX - 9）和骨相关分子（骨钙素、cbfalpha - 1）表达的增加表明，在骨修复过程中，软骨内成骨和直接骨形成机制均有参与。
