title: Role and regulation of VEGF and its receptors 1 and 2 in the aseptic loosening of total hip implants.
abstract: It was hypothesized that vascular endothelial growth factor (VEGF) in fibroblasts participates in aseptic loosening of total hip replacement (THR) implants. Therefore, osteoarthritic (OA) samples (n = 11) were compared with synovial membrane-like interface tissues from revision THR (n = 10). VEGF-A and its receptors were stained using streptavidin-immunoperoxidase method. Their regulation by hypoxia and cytokines were studied in cultured fibroblasts using quantitative real-time polymerase chain reaction (qRT-PCR). VEGFR1(+) lining cells (p < 0.01), stromal fibroblast-like cells (p = 0.001) and stromal macrophage-like cells (p < 0.05) were more numerous in rTHR than in OA. As to VEGFR2(+), only stromal fibroblast-like cells in rTHR outnumbered those found in OA (p < 0.05). VEGFRs in synovial fibroblasts were not affected by hypoxia, but VEGF increased 2.4-fold (p < 0.05). Interleukin-4 up-regulated VEGFR1 expression 23-fold. This is the first study to describe a difference between rTHR and OA in VEGF receptors, particularly VEGFR1. Hypoxia increased VEGF, but the VEGFR1 increase in the lining and stroma is probably IL-4 driven, in accordance with the M2-type macrophage dominance in interface tissues. VEGF/VEGFR system is also affected by hypoxia and may play a role in angiogenesis and bone pathology in aseptic loosening of total hip implants.
authors.affiliation: Mikkeli Central Hospital, 50100 Mikkeli, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Waris
authors.forename: Tarvo
authors.initials: T
authors.lastname: Sillat
authors.forename: Eero
authors.initials: E
authors.lastname: Waris
authors.forename: Liisa
authors.initials: L
authors.lastname: Virkki
authors.forename: Jami
authors.initials: J
authors.lastname: Mandelin
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takagi
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000368:Aged; D000818:Animals; D019644:Arthroplasty, Replacement, Hip; D002460:Cell Line; D016207:Cytokines; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000378:metabolism / Q000473:pathology; D011475:Prosthesis Failure; D011817:Rabbits; D012086:Reoperation; D013583:Synovial Membrane / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2