tailieunhanh - báo cáo hóa học:" Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học quốc tế đề tài : Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone | Matsumoto et al. Journal of Orthopaedic Surgery and Research 2010 5 85 http content 5 1 85 JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH RESEARCH ARTICLE Open Access Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone Yoshihiro Matsumoto Yuko Okada Jun-ichi Fukushi Satoshi Kamura Toshifumi Fujiwara Keiichiro lida Mihoko Koga Shuichi Matsuda Katsumi Harimaya Akio Sakamoto Yukihide Iwamoto Abstract Background Giant cell tumors GCTs of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells MNCs . Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells while monocyte-like cells and MNCs are reactive osteoclast precursor cells OPCs and osteoclasts OCs respectively. In this study we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor VEGF -Flt-1 type-1 VEGF receptor -focal adhesion kinase FAK pathway. Methods The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry. Results In GCT samples CD68 a marker of OPCs and OCs co-localized with Flt-1. Conditioned media from GCT tissue GCT-CM enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK. Conclusions Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs. Background Giant .