Connective tissue growth factor and insulin-like growth factor 2 show upregulation in early growth plate radiorecovery response following irradiation.
Connective tissue growth factor and insulin-like growth factor 2 show upregulation in early growth plate radiorecovery response following irradiation.
复制标题
结缔组织生长因子和胰岛素样生长因子 2 在照射后的早期生长板放射恢复反应中表现出上调。
DOI：
10.1159/000105673
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Damron,TimothyA
中科院分区：
文献类型：
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作者：
Wang,Yan;Zhang,Mingliang;Middleton,FrankA;Horton,JasonA;Pritchard,Meredith;Spadaro,JosephA;Farnum,CorneliaE;Damron,TimothyA
前言：放射治疗后的生长板反应知之甚少。特别是，人们对照射后生长板生长因子和细胞因子的变化知之甚少。假设生长因子和细胞因子在生长板增殖和肥大的软骨细胞放射修复中起作用。方法：6只大鼠的右肢接受17.5Gy射线照射，左侧肢体作为对照。术后1周(n=3)和2周(n=3)取肢。从正常和照射的胫骨生长板的增殖区(PZ)和肥大区(HZ)用激光显微切割获得的软骨细胞构建微阵列。实时定量聚合酶链式反应检测甲状旁腺激素受体1、结缔组织生长因子1、胰岛素样生长因子I受体、胰岛素样生长因子2、白细胞介素17β和趋化因子配体12的表达。结果与结论：照射后1周，未成熟动物模型生长板恢复前，甲状旁腺激素受体1、结缔组织生长因子1、胰岛素样生长因子1受体、胰岛素样生长因子2、白细胞介素17受体和趋化因子配体12均上调。照射后2周，两区CTGF和Pth1，PZ区CXCL12及其受体，HZ区IL17b和骨形态发生蛋白2等生长因子和细胞因子表达上调，提示辐射恢复可能在后期起作用。通过基因芯片和实时荧光RT-PCR法检测，辐射对PZ中Pth1、CTGF、IGF2和CXCL12的影响与HZ中Pth1、CTGF、IL17b和IGF1R的变化高度相关(PZ和HZ的相关系数分别为0.797、0.875和0.01)。
Introduction:The growth plate response following radiotherapy is poorly understood. In particular, little is known about the changes in growth plate growth factors and cytokines following irradiation. The hypothesis was that a limited number of growth factors and cytokines play a role in growth plate proliferative and hypertrophic chondrocyte radio-recovery.Methods:The right limbs of 6 rats were irradiated (17.5 Gy), leaving the left limbs as controls. Limbs were harvested 1 (n = 3) and 2 (n = 3) weeks later. Microarrays were constructed from chondrocytes obtained by laser microdissection from the proliferative zone (PZ) and the hypertrophic zone (HZ) of normal and irradiated tibia growth plates. Real-time PCR was used to confirm the expression of parathyroid hormone receptor 1 (Pthr1), connective tissue growth factor (CTGF), insulin-like growth factor I receptor (IGF1R), insulin-like growth factor II (IGF2), interleukin 17β (IL17b) and chemokine ligand 12 (CXCL12).Results and Conclusions:IGF2 is upregulated in the PZ and CTGF is upregulated in both the PZ and HZ 1 week after irradiation, prior to the histomorphometric appearance of growth plate recovery in this immature animal radiation model, supporting their role in stimulating early return of the growth plate. By 2 weeks after irradiation, a number of growth factors and cytokines, including CTGF and Pthr1 in both zones, CXCL12 and its receptor in the PZ, and IL17b and bone morphogenetic protein 2 in the HZ, show upregulation, suggesting a possible later role in radiorecovery. The effects of irradiation on Pthr1, CTGF, IGF2 and CXCL12 in PZ and Pthr1, CTGF, IL17b and IGF1R in the HZ determined by microarray and real-time RT-PCR was highly correlated (r = 0.797, p < 0.05 in the PZ and r = 0.875, p < 0.01 in the HZ, respectively).