Osteopontin induces vascular endothelial growth factor expression in articular cartilage through PI3K/AKT and ERK1/2 signaling

被引:46
作者
Xu, Jun [1 ]
Yi, Yu [1 ]
Li, Lin [2 ]
Zhang, Weiguo [1 ]
Wang, Jianhua [3 ]
机构
[1] Huazhong Univ Sci & Technol, Wuhan Cent Hosp, Dept Orthoped Surg, Wuhan 430030, Hubei, Peoples R China
[2] Huazhong Univ Sci & Technol, Wuhan Cent Hosp, Dept Neurol, Wuhan 430030, Hubei, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Orthoped Surg, Shanghai 200092, Peoples R China
基金
中国国家自然科学基金;
关键词
osteoarthritis; articular cartilage; osteopontin; angiogenesis; extracellular signal-regulated kinase/2 pathway; phosphoinositide 3-kinase/AKT pathway; vascular endothelial growth factor; FACTOR VEGF; TUMOR PROGRESSION; OSTEOARTHRITIS; ANGIOGENESIS; ETIOLOGY; CHONDROCYTES; GENETICS; MODELS; CELLS; KNEE;
D O I
10.3892/mmr.2015.3975
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
The expression of osteopontin (OPN) and vascular endothelial growth factor (VEGF) are associated with the severity of cartilage destruction in osteoarthritis. However, the biological connection between OPN and VEGF in osteoarthritis remains to be elucidated. The present study was performed to investigate the effect of OPN on VEGF expression in articular cartilage. Rat articular chondrocytes were isolated and cultured in monolayer conditions, and they were treated with OPN for different time periods (0, 2, 8, 12 or 24 h) and dosages (0, 0.1, 0.25 or 0.5 mu M). VEGF expression was assessed by reverse transcription-quantitative polymerase chain reaction and western blotting. The activation of the phosphoinositide 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK) 1/2 pathway was analyzed by detecting the expression of pPI3K, pAKT and pERK1/2. To inhibit the PI3K/AKT and ERK1/2 pathway, LY294002 and PD98059 were used, respectively or in combination. It was identified that OPN increased the expression of VEGF in a dose-and time-dependent manner. The PI3K/AKT and ERK1/2 pathways were activated following OPN stimulation and the effect was concomitant with the upregulation of VEGF. Finally, the regulation of VEGF was inhibited by LY294002 and PD98059, and their combination exhibited a synergistic effect. In conclusion, these findings suggest that OPN may directly upregulate VEGF expression through the PI3K/AKT and ERK1/2 pathway. Further studies are required to reveal the mechanism of action of OPN on cartilage angiogenesis and cartilage destruction.
引用
收藏
页码:4708 / 4712
页数:5
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