The hypoxic synovial environment regulates expression of vascular endothelial growth factor and osteopontin in juvenile idiopathic arthritis
Bosco MC et al. – Study demonstrates that the hypoxic synovial monocytic cells are a likely source of vascular endothelial growth factor (VEGF) and osteopontin (OPN) in juvenile idiopathic arthritis (JIA). Methods- Aim was to characterized the contribution of the local hypoxic environment to VEGF and OPN production by monocytic cells recruited to the synovium in JIA
- Paired synovial fluid (SF) and peripheral blood (PB) samples were collected from 20 pts with JIA
- Mononuclear cells (MC) were isolated, and monocytic cells were purified by adherence, maintained in a hypoxic environment, or subjected to reoxygenation
- VEGF and OPN protein concns were tested in SF, plasma, and culture supernatants
- Synovial tissue was obtained at synovectomy from 4 pts with JIA, and analyzed by IHC for VEGF, OPN, CD68, and HIF-1α
Results- VEGF mRNA expression was increased in SFMC and SF monocytic cells vs matched PBMC and PB monocytic cells or SF lymphocytes; correlated with higher protein levels
- OPN mRNA expression in SF monocytic cells was associated with increase of SF protein
- IHC revealed the presence of both factors in synovial tissues at the level of the lining and sublining layers
- This colocalized with intense CD68 and HIF-1α staining, suggesting production by hypoxic synovial monocytic cells
- VEGF and OPN expression was abrogated upon SF monocytic cell reoxygenation and maintained by exposure to prolonged hypoxia
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