The effectof age on gene expression in adult and juvenile rats following femoral fracture
The effectof age on gene expression in adult and juvenile rats following femoral fracture
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DOI：
10.1097/00005131-200311000-00005
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发表时间：
2003-11-01
影响因子：
2.3
通讯作者：
Meyer, RA
中科院分区：
文献类型：
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作者：
Desai, BJ;Meyer, MH;Meyer, RA
目的：比较幼年和成年大鼠骨折愈合过程中的基因表达。设计：在6周龄和26周龄大鼠的骨折后0周、1周、2周、4周、6周、8周和10周(6只大鼠/年龄/时间点)检测基因表达。地点：AAALAC认证的独立学术医学中心的外阴组织。动物：6周龄和26周龄的雌性SD大鼠。干预：在左侧股骨逆行放置髓内棒，造成单纯的横断性闭合性骨干中骨折。主要结果测量：细胞外基质、成骨细胞、成骨细胞的34个基因的基因表达结果：幼年大鼠骨折后4周达到放射学愈合，而成年大鼠需要8~10周才能愈合。所有研究基因的mRNA表达均在骨折后1~2周达到高峰。然后，年轻大鼠的所有基因在骨折后4周降至基线水平。然而，在成年大鼠放射学愈合所需的较长时间内，只有与骨基质、成骨细胞标志物、血管生成和成纤维细胞生长因子相关的基因在骨折后4周和6周仍显著上调。在成年大鼠的骨折愈合过程中，软骨、印度刺猬、骨形态发生蛋白和转化生长因子-β的相关基因在放射学联合前达到了检测不到的基线值。结论：大多数骨愈合刺激因子在成年大鼠骨折修复的后期不表达。其他基因必须控制骨骼生长，以弥合骨折缺口。
Objective: To compare mRNA gene expression during fracture healing in young and adult rats.Design: Gene expression was measured at zero, 1, 2, 4, 6, 8 and 10 weeks after fracture (6 rats/age/time point) in rats at 6 and 26 weeks of age at surgery.Setting: AAALAC-accredited vivarium of an independent academic medical center.Animals: Female Sprague-Dawley rats at 6 and 26 weeks of age.Intervention: An intramedullary rod was placed retrograde in the left femur, and a simple transverse closed middiaphyseal fracture was induced.Main Outcome Measurements: mRNA gene expression was measured for 34 genes for extracellular matrix, osteoblasts, bone morphogenic protein, inflammation, cytokine, and receptor genes.Results: The young rats reached radiographic union by 4 weeks after fracture, whereas the adult rats took 8 to 10 weeks to unite. All genes studied increased in mRNA expression with a peak at 1 to 2 weeks after fracture. All genes in the young rats then subsided to baseline by 4 weeks after fracture. However, during the longer period needed for radiographic union in the adult rats, only genes related to bone matrix, osteoblastic markers, angiogenesis, and the fibroblast growth factors remained significantly up-regulated at 4 and 6 weeks after fracture. Genes related to cartilage, Indian hedgehog, the bone morphogenctic proteins, and transforming growth factor-beta came to undetectable baseline values in the adult rats prior to radiographic union.Conclusions: Most stimulators of bone healing are not expressed during the later stages of fracture repair in adult rats. Other genes must control bone growth to bridge the fracture gap.