Huang Jiang, Liu Liming, Feng Mingli, An Shuai, Zhou Meng, Li Zheng, Qi Jiajian, Shen Huiliang
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Mol Med Rep. 2015 Oct;12(4):5951-6. doi: 10.3892/mmr.2015.4122. Epub 2015 Jul 27.
Low oxygen availability is known to activate the hypoxia-inducible factor-1α (HIF-1α) pathway, which is involved in the impairment of fracture healing. However, the role of low oxygen in fracture healing remains to be fully elucidated. In the present study, rats were divided into two groups and treated with CoCl2 or saline, respectively. Mice with tibial fractures were sacrificed at 14, 28 and 42 days subsequent to fracture. Autoradiography was performed to measure healing of the bone tissue. In addition, the effects of cobalt chloride (CoCl2) on the expression of two major angiogenic mediators, HIF‑1α and vascular endothelial growth factor (VEGF), as well as the osteoblast markers runt‑related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OC) were determined at mRNA and protein levels by reverse transcription‑quantitative polymerase chain reaction, western blot analysis and immunohistochemistry. Systemic administration of CoCl2 (15 mg/kg/day intraperitoneally) significantly promoted fracture healing and mechanical strength. The present study demonstrated that in rats treated with CoCl2, the expression of HIF‑1α, VEGF, Runx2, ALP and OC was significantly increased at mRNA and protein levels, and that CoCl2 treatment enhances fracture repair in vivo.
已知低氧可激活缺氧诱导因子-1α（HIF-1α）通路，该通路与骨折愈合受损有关。然而，低氧在骨折愈合中的作用仍有待充分阐明。在本研究中，将大鼠分为两组，分别用氯化钴或生理盐水处理。在骨折后的第14、28和42天处死胫骨骨折的小鼠。进行放射自显影以测量骨组织的愈合情况。此外，通过逆转录-定量聚合酶链反应、蛋白质印迹分析和免疫组织化学在mRNA和蛋白质水平上测定了氯化钴（CoCl2）对两种主要血管生成介质HIF-1α和血管内皮生长因子（VEGF）以及成骨细胞标志物 runt相关转录因子2（Runx2）、碱性磷酸酶（ALP）和骨钙素（OC）表达的影响。全身给予CoCl2（15 mg/kg/天，腹腔注射）可显著促进骨折愈合和机械强度。本研究表明，在用CoCl2处理的大鼠中，HIF-1α、VEGF、Runx2、ALP和OC的表达在mRNA和蛋白质水平上显著增加，并且CoCl2处理可增强体内骨折修复。
