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Arthritis Rheum. 2011 Nov;63(11):3243-52. doi: 10.1002/art.30564.

Nerve growth factor: A key local regulator in the pathogenesis of inflammatory arthritis.

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University of California School of Medicine, Davis, VA Medical Center, Sacramento, California, USA.



The effect of nerve growth factor (NGF) and its receptor (NGFR) in inflammatory diseases is a novel research field. The purpose of this study was to investigate the role of NGF/NGFR in human T cell subpopulations and fibroblast-like synovial cells (FLS) and examine its pathophysiologic significance in psoriatic arthritis (PsA) and rheumatoid arthritis (RA).


Expression of NGF/NGFR was examined in synovial fluid (SF), FLS, peripheral blood (PB)-derived T cells, and SF-derived T cells from patients with PsA, RA, and osteoarthritis (OA). NGF levels were determined by enzyme-linked immunosorbent assay. NGF-induced T cell/FLS proliferation was examined by MTT assay. Low-affinity (p75)/high-affinity (TrkA) NGFR expression was determined by high-dimensional fluorescence-activated cell sorting. A monochlorobimane assay was used to determine the effect of NGF on T cell survival.


Levels of NGF were higher in SF samples from PsA and RA patients as compared to SF samples from OA patients. NGF-induced FLS proliferation was more marked in PsA and RA patients. TrkA was up-regulated on activated SF T cells from PsA (mean ± SD 22 ± 6.2%) and RA (8 ± 1.3%) patients, whereas in SF samples from OA patients, TrkA+CD3+ T cells were not detectable. NGF induced the proliferation of PB T cells, induced the phosphorylation of Akt in activated T cells, and consistent with known pAkt activity, inhibited tumor necrosis factor α-induced cell death in these T cells.


Based on our findings, we propose a model in which NGF secreted by FLS into PsA and RA synovium promotes the survival of activated autoreactive T cells as well as FLS proliferation. Thus, NGF has the potential to sustain the chronic inflammatory cascades of arthritis of autoimmune origin.

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