Egr-1 increases angiogenesis in cartilage via binding Netrin-1 receptor DCC promoter.

Abstract

Osteoarthritis (OA) is a joint disease characterized by degradation of cartilage. The etiology of OA is still unclear. Vascular endothelial growth factor (VEGF) plays a key role of angiogenesis in the pathogenesis of OA and contributes to the angiogenesis of NT-1/DCC. Whether or not NT-1/DCC and VEGF interact in regulating angiogenesis of OA cartilage is not known. Histological studies for CD34, VEGF, and safranin-O staining were performed to determine angiogenesis and cartilage tissue injury. ELISA indicated the level of pro-inflammation cytokines. Immunoblotting, immunoprecipitation, and electrophoretic mobility shift assay (EMSA) were performed to assay the expression and function of NT-1/DCC-VEGF signaling pathway. Our data indicated that VEGF expression was increased in cartilage tissue from OA rats, while the chondrocytes were disorganized, and cartilage degeneration was increasing in OA rats. The inflammation factors in articular cavity fluid were higher in the OA rats than in the sham. The protein expression of NT-1, DCC, and VEGF were increased in osteoarthritic cartilage. DCC was involved in the positive regulation of osteoarthritic angiogenesis by VEGF. Egr-1 expression was higher in OA rats than in sham rats. Egr-1 is a regulator of DCC promoter activity, and the binding is higher in OA rats than in sham rats. Our present study provides a mechanism by which Egr-1 induced angiogenesis via NT-1/DCC-VEGF pathway.