Rheumatology Medical News about juvenile idiopathic arthritis;hypoxic synovial environment;expression of vascular endothelial growth factor;osteopontin

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The hypoxic synovial environment regulates expression of vascular endothelial growth factor and osteopontin in juvenile idiopathic arthritis
Journal of Rheumatology, 06/11/09

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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