title: Platelet-rich plasma increases matrix metalloproteinases in cultures of human synovial fibroblasts.
abstract: BACKGROUND
  The effect of platelet-rich plasma on chondrocytes has been studied in cell and tissue culture. Less attention has been given to the effect of platelet-rich plasma on nonchondrocytic cell lineages within synovial joints, such as fibroblast-like synoviocytes, which produce cytokines and matrix metalloproteinases (MMPs) that mediate cartilage catabolism. The purpose of the present study was to determine the effect of platelet-rich plasma on cytokines and proteases produced by fibroblast-like synoviocytes.
  
  
  METHODS
  Platelet-rich plasma and platelet-poor plasma from harvested autologous blood were prepared with a commercially available system. Fibroblast-like synoviocytes were treated with platelet-rich plasma, platelet-poor plasma, recombinant PDGFββ (platelet-derived growth factor ββ), or phosphate-buffered saline solution and incubated at 37°C for forty-eight hours. The concentrations of IL-1β (interleukin-1β), IL-1RA (IL-1 receptor antagonist), IL-6, IFN-γ (interferon-γ), IP-10 (interferon gamma-induced protein 10), MCP-1 (monocyte chemotactic protein-1), MIP-1β (macrophage inflammatory protein-1β), PDGFββ, RANTES, TNF-α (tumor necrosis factor-α), VEGF (vascular endothelial growth factor), MMP-1, MMP-3, and MMP-9 in the culture medium were determined by multiplex immunoassay.
  
  
  RESULTS
  Platelet-rich plasma cultured in medium contained multiple catabolic mediators in substantial concentrations, including MMP-9 (15.8 ± 2.3 ng/mL) and MMP-1 (2.5 ± 0.8 ng/mL), as well as proinflammatory mediators IL-1β, IL-6, IFN-γ, IP-10, MCP-1, MIP-1β, RANTES, and TNF-α in concentrations between 20 pg/mL and 20 ng/mL. Platelet-poor plasma contained significantly lower concentrations of these compounds. Platelet-rich plasma was used to treat human fibroblast-like synoviocytes, and the resulting concentrations of mediators were corrected for the concentrations in the platelet-rich plasma alone. Compared with untreated fibroblast-like synoviocytes, synoviocytes treated with platelet-rich plasma exhibited significantly greater levels of MMP-1 (363 ± 94.0 ng/mL, p = 0.018) and MMP-3 (278 ± 90.0 ng/mL, p = 0.018). In contrast, platelet-poor plasma had little effect on mediators secreted by the synoviocytes. PDGFββ-treated fibroblast-like synoviocytes exhibited a broad proinflammatory cytokine response at four and forty-eight hours.
  
  
  CONCLUSIONS
  Platelet-rich plasma was shown to contain a mixture of anabolic and catabolic mediators. Synoviocytes treated with platelet-rich plasma responded with substantial MMP secretion, which may increase cartilage catabolism. Synoviocytes responded to PDGF with a substantial proinflammatory response.
authors.affiliation: Cytonics Corporation, 555 Heritage Drive, Suite 115, Jupiter, FL 33458, USA.
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Browning
authors.forename: Amiee M
authors.initials: AM
authors.lastname: Weiser
authors.forename: Naruewan
authors.initials: N
authors.lastname: Woolf
authors.forename: S Raymond
authors.initials: SR
authors.lastname: Golish
authors.forename: Thomas P
authors.initials: TP
authors.lastname: SanGiovanni
authors.forename: Gaetano J
authors.initials: GJ
authors.lastname: Scuderi
authors.forename: Carolina
authors.initials: C
authors.lastname: Carballo
authors.forename: Lewis S
authors.initials: LS
authors.lastname: Hanna
mesh_terms: D000328:Adult; D016512:Ankle Injuries / Q000000981:diagnostic imaging / Q000601:surgery; D001182:Arthroscopy / Q000379:methods; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000601:surgery; D006801:Humans; D007719:Knee Joint / Q000503:physiopathology / Q000601:surgery; D008297:Male; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D053657:Platelet-Rich Plasma; D011859:Radiography; D012016:Reference Values; D012680:Sensitivity and Specificity; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D020782:Matrix Metalloproteinases