Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients.
OBJECTIVE
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-1beta (IL-1beta) 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-beta1(TGF-beta1), 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-beta1 levels remained unchanged. PRGF significantly enhanced the secretion of HA induced by IL-1beta activation, P < 0.05, but it did not modify the IL-1beta-induced rise in MMP-1, MMP-3 and VEGF. In contrast, PRGF-induced HGF production was abolished by the presence of IL-1beta 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-1beta on synovial cells.
Anitua
E
E
Biotechnology Institute, BTI IMASD, Vitoria, Spain.
Sánchez
M
M
Nurden
A T
AT
Zalduendo
M M
MM
de la Fuente
M
M
Azofra
J
J
Andía
I
I
D000368:Aged; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy / Q000473:pathology; D011336:Probability; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000166:cytology; D013939:Thymidine Phosphorylase / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D006820:Hyaluronic Acid; D013939:Thymidine Phosphorylase