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Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients

Objectives. Autologous platelet-secreted growth factors (GFs) may have therapeutic effects in osteoarthritis (OA) capsular joints via multiple mechanisms. Our aim was to examine the effect of a platelet-derived preparation rich in growth factors (PRGFs) in OA synovial cell biology.

Methods. Synovial cells were isolated from 10 osteoarthritic patients and cultured in serum-free media (basal conditions) and exposed to either a platelet-poor preparation or PRGF for 72 h. Cells activated with interleukin-1ß (IL-1ß) for 48 h were also exposed to PRGF. Changes in several events relevant to joint homeostasis including (i) hyaluronic acid (HA) secretion, (ii) the balance between metalloproteinase-1, -3 and -13 (MMP-1, MMP-3 and MMP-13) and tissue inhibitor-1 (TIMP-1) and (iii) the secretion of transforming growth factor-ß1(TGF-ß1), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), were all assessed.

Results.
PRGF significantly enhanced HA secretion compared with platelet-poor preparations, P < 0.05; at the same time release of TIMP-1, MMP-1, MMP-3 and MMP-13 were not affected. An increased HGF production was observed (P < 0.05) but VEGF and TGF-ß1 levels remained unchanged. PRGF significantly enhanced the secretion of HA induced by IL-1ß activation, P < 0.05, but it did not modify the IL-1ß-induced rise in MMP-1, MMP-3 and VEGF. In contrast, PRGF-induced HGF production was abolished by the presence of IL-1ß during PRGF treatment, P < 0.05.

Conclusions. Intra-articular administration of PRGF might be beneficial in restoring HA concentration and switching angiogenesis to a more balanced status but does not halt the effects of IL-1ß on synovial cells.

Published on 05-27-2009
Authors: E. Anitua, M. Sanchez1, A. T. Nurden2, M. M. Zalduendo, M. de la Fuente, J. Azofra1 and I. Andia
Source: Rheumatology Advance Access published online on October 17, 2007