title: Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine chondrocytes through activation of PPAR-gamma.
abstract: It has been reported that vascular endothelial growth factor (VEGF) and its receptors play an important role in the destruction of articular cartilage in osteoarthritis through increased production of matrix metalloproteinases. We investigated whether the oxidized low-density lipoprotein (ox-LDL) binding to lectin-like ox-LDL receptor-1 (LOX-1) upregulates VEGF expression in cultured bovine articular chondrocytes (BACs). Ox-LDL markedly increased VEGF mRNA expression and protein release in time- and dose-dependent manners, which was significantly suppressed by anti-LOX-1 antibody pretreatment. Activation of peroxisome proliferator-activated receptor (PPAR)-gamma was evident in BACs with ox-LDL addition and was attenuated by anti-LOX-1 antibody. The specific PPAR-gamma inhibitor GW9662 suppressed ox-LDL-induced VEGF expression. These results suggest that the ox-LDL/LOX-1 system upregulates VEGF expression in articular cartilage, at least in part, through activation of PPAR-gamma and supports the hypothesis that ox-LDL is involved in cartilage degradation via LOX-1.
authors.affiliation: Department of Orthopaedic Surgery, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka, 589-8511, Japan.
authors.forename: Sohya
authors.initials: S
authors.lastname: Kanata
authors.forename: Masao
authors.initials: M
authors.lastname: Akagi
authors.forename: Shunji
authors.initials: S
authors.lastname: Nishimura
authors.forename: Sumio
authors.initials: S
authors.lastname: Hayakawa
authors.forename: Kohji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Munakata
authors.forename: Chiaki
authors.initials: C
authors.lastname: Hamanishi
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005786:Gene Expression Regulation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000378:metabolism* / Q000502:physiology; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008077:Lipoproteins, LDL; D047495:PPAR gamma; D051127:Scavenger Receptors, Class E; D042461:Vascular Endothelial Growth Factor A; C099252:oxidized low density lipoprotein