Production of VEGF receptor 1 and 2 mRNA and protein during endochondral bone repair is differential and healing phase specific.
Production of VEGF receptor 1 and 2 mRNA and protein during endochondral bone repair is differential and healing phase specific.
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DOI：
10.1152/japplphysiol.00839.2010
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发表时间：
2010-10
影响因子：
3.3
通讯作者：
M. Reumann;Turya Nair;Olga Strachna;A. Boskey;P. Mayer‐Kuckuk
中科院分区：
文献类型：
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作者：
M. Reumann;Turya Nair;Olga Strachna;A. Boskey;P. Mayer‐Kuckuk
包括暂时性缺氧在内的生理干扰预计会在骨修复期间驱动血管生成。有证据表明，血管生成配体血管内皮生长因子（VEGF）-A在这一过程中发挥了重要作用。在小鼠肋骨骨折模型中，我们表征了两种对介导VEGF信号传导至关重要的受体VEGFR 1/Flt-1和VEGFR 2/Flk-1/KDR的表达。他们的mRNA和蛋白质水平进行了评估，在四个愈合阶段，其特点是出血形成骨折后第一天（PFD）1，炎症反应PFD 3，开始愈伤组织发展PFD 7，并在PFD 14成熟愈伤组织的存在。检测VEGFR 1和VEGFR 2以及VEGF的转录物。虽然VEGF 1的mRNA表达在所有愈合阶段都是双相的，但VEGF 2在愈伤组织形成和成熟过程中表现出明显增加的mRNA表达的双相特征。在愈伤组织形成过程中VEGF mRNA的表达呈逐渐增加的趋势。VEGFR 1的蛋白质水平在初始愈合阶段低于检测灵敏度。然后恢复到稳定的水平，通过随后的愈合阶段可以检测到。因此，VEGFR 1蛋白水平部分反映了转录本表达谱。相比之下，VEGFR 2的蛋白水平在愈合阶段逐渐增加，并在愈伤组织成熟时达到峰值。这与VEGFR 2的转录表达密切相关。来自年龄匹配的雄性小鼠的完整骨具有相当高的VEGFR 1和VEGF蛋白水平，但检测不到VEGFR 2。总之，这些发现揭示了VEGF-VEGFR轴在软骨内骨修复中的表达特征。
Physiological disturbances, including temporary hypoxia, are expected to drive angiogenesis during bone repair. Evidence suggests that the angiogenic ligand vascular endothelial growth factor (VEGF)-A plays an important role in this process. We characterized the expression of two receptors that are essential for mediating VEGF signaling, VEGFR1/Flt-1 and VEGFR2/Flk-1/KDR, in a mouse rib fracture model. Their mRNA and protein levels were assessed in four healing phases, which were characterized histologically as hemorrhage formation on postfracture day (PFD) 1, inflammatory response on PFD 3, initiation of callus development on PFD 7, and the presence of a mature callus on PFD 14. Transcript was detected for VEGFR1 and VEGFR2, as well as VEGF. While mRNA expression of VEGFR1 was monophasic throughout all healing phases, VEGFR2 showed a biphasic profile with significantly increased mRNA expression during callus formation and maturation. Expression of VEGF mRNA was characterized by a more gradual increase during callus formation. The protein level for VEGFR1 was below detection sensitivity during the initial healing phase. It was then restored to a stable level, detectable through the subsequent healing phases. Hence, the VEGFR1 protein levels partially mirrored the transcript expression profile. In comparison, the protein level of VEGFR2 increased gradually during the healing phases and peaked at callus maturation. This correlated well with the transcriptional expression of VEGFR2. Intact bone from age-matched male mice had considerable protein levels of VEGFR1 and VEGF, but no detectable VEGFR2. Together, these findings uncovered expression signatures of the VEGF-VEGFR axis in endochondral bone repair.