Low-dose X-ray irradiation promotes osteoblast proliferation, differentiation and fracture healing.

Low-dose X-ray irradiation promotes osteoblast proliferation, differentiation and fracture healing.
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低剂量 X 射线照射促进成骨细胞增殖、分化和骨折愈合

DOI:
10.1371/journal.pone.0104016
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Ling M
Ling M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen M;Huang Q;Xu W;She C;Xie ZG;Mao YT;Dong QR;Ling M

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关于成骨细胞对x射线照射的生物学反应存在很大争议,其机制尚不清楚。在本研究中,通过体外细胞培养和体内动物实验,确定了低剂量辐射刺激成骨细胞增殖、分化和骨折愈合的生物学效应。首先,低剂量(0.5 Gy) x射线照射诱导MC3T3-E1细胞活力和增殖。然而,高剂量(5gy) x射线照射抑制成骨细胞的活力和增殖。此外,通过Western blot分析,观察低剂量和高剂量照射后成骨细胞分化标志物I型胶原、碱性磷酸酶、Runx2、Osterix和骨钙素的动态变化。其次,单剂量x线照射后通过组织学和基因表达评价骨折愈合情况,低剂量x线照射可促进闭合性股骨骨折大鼠骨折愈合。在低剂量x射线照射骨折中,观察到增殖细胞核抗原(PCNA)阳性细胞,软骨形成和骨折老茧的增加。此外,我们观察到更快完成软骨内和膜内骨化,这伴随着参与骨重塑和骨折愈伤组织矿化的基因表达的改变。虽然高剂量照射大鼠骨折骨痂中几种成骨细胞分化基因的表达水平升高,但与对照组和低剂量照射骨折相比,骨痂形成和骨折愈合延迟。这些结果揭示了低剂量辐射的有益作用,包括刺激成骨细胞增殖、分化和骨折愈合,并强调了其在骨相关疾病新疗法中的潜在转化应用。
Great controversy exists regarding the biologic responses of osteoblasts to X-ray irradiation, and the mechanisms are poorly understood. In this study, the biological effects of low-dose radiation on stimulating osteoblast proliferation, differentiation and fracture healing were identified using in vitro cell culture and in vivo animal studies. First, low-dose (0.5 Gy) X-ray irradiation induced the cell viability and proliferation of MC3T3-E1 cells. However, high-dose (5 Gy) X-ray irradiation inhibited the viability and proliferation of osteoblasts. In addition, dynamic variations in osteoblast differentiation markers, including type I collagen, alkaline phosphatase, Runx2, Osterix and osteocalcin, were observed after both low-dose and high-dose irradiation by Western blot analysis. Second, fracture healing was evaluated via histology and gene expression after single-dose X-ray irradiation, and low-dose X-ray irradiation accelerates fracture healing of closed femoral fractures in rats. In low-dose X-ray irradiated fractures, an increase in proliferating cell nuclear antigen (PCNA)-positive cells, cartilage formation and fracture calluses was observed. In addition, we observed more rapid completion of endochondral and intramembranous ossification, which was accompanied by altered expression of genes involved in bone remodeling and fracture callus mineralization. Although the expression level of several osteoblast differentiation genes was increased in the fracture calluses of high-dose irradiated rats, the callus formation and fracture union were delayed compared with the control and low-dose irradiated fractures. These results reveal beneficial effects of low-dose irradiation, including the stimulation of osteoblast proliferation, differentiation and fracture healing, and highlight its potential translational application in novel therapies against bone-related diseases.
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期刊: RADIATION RESEARCH
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