The regulatory role of nerve growth factor and its receptor system in fibroblastlike synovial cells

Objectives Investigating the role of nerve growth factor NGF and its receptors NGFR in inflammatory diseases is an active field of research. Inflammatory diseases of the joint are the commonest cause of human morbidity but very little is known about the effect of NGF on synovial tissue biology. Here we have studied NGFNGFR and their functional significance on cultured fibroblastlike synovial cells FLS collected from the synovial tissue of five healthy subjects. Methods NGFNGFR expression was determined in the basal condition and after stimulation with tumour necrosis factor TNF and interleukin IL1 by enzymelinked immunosorbent assay ELISA and fluorescenceactivated cell sorting FACS. Proliferation studies were performed by cell count, hexosaminidase assay, and the MTT assay. The synovial fluid SF NGF level was studied by ELISA in 12 psoriatic arthritis PsA, 14 rheumatoid arthritis RA, and 10 osteoarthritis OA patients. Results FACS studies showed that unstimulated FLS expressed low levels of NGF and the highaffinity NGFtyrosine kinase receptor TrkA, and TNF and IL1 increased NGF and TrkA expression in FLS. NGF 100ngmL increased FLS proliferation by 400 compared to the control medium only. The NGF level was significantly higher in the PsA group 365.5±85.2pgmL than in the RA 120±35pgmL and OA groups 30±6pgmL. Conclusions Upregulation of NGFTrkA in proinflammatory cytokineactivated FLS, the mitogenic effect of NGF on FLS, and the increased NGF level in SF of inflammatory arthritis suggest that there is crosstalk between NGFNGFR and FLS. These results also suggest that dysregulated production of NGF may lead to synovial cell proliferation and thus could influence the inflammatory and proliferative cascades of inflammatory arthritis.