Autologous Protein Solution Inhibits MMP-13 Production by IL-1β and TNFα-stimulated Human Articular Chondrocytes

J Orthop Res. 2011 Sep;29(9):1320-6. doi: 10.1002/jor.21384. Epub 2011 Mar 15.

Abstract

Catabolic inflammatory cytokines are prevalent in osteoarthritis (OA). The purpose of this study was to evaluate an autologous protein solution (APS) as a potential chondroprotective agent for OA therapy. APS was prepared from platelet-rich plasma (PRP). The APS solution contained both anabolic (bFGF, TGF-β1, TGF-β2, EGF, IGF-1, PDGF-AB, PDGF-BB, and VEGF) and anti-inflammatory (IL-1ra, sTNF-RI, sTNF-RII, IL-4, IL-10, IL-13, and IFNγ) cytokines but low concentrations of catabolic cytokines (IL-1α, IL-1β, TNFα, IL-6, IL-8, IL-17, and IL-18). Human articular chondrocytes were pre-incubated with the antagonists IL-1ra, sTNF-RI, or APS prior to the addition of recombinant human IL-1β or TNFα. Following exposure to inflammatory cytokines, the levels of MMP-13 in the culture medium were evaluated by ELISA. MMP-13 production stimulated in chondrocytes by IL-1β or TNFα was reduced by rhIL-1ra and sTNF-RI to near basal levels. APS was also capable of inhibiting the production of MMP-13 induced by both IL-1β and TNFα. The combination of anabolic and anti-inflammatory cytokines in the APS created from PRP may render this formulation to be a potential candidate for the treatment of inflammation in patients at early stages of OA.

MeSH terms

  • Blood Proteins / pharmacology*
  • Cartilage, Articular / cytology
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Drug Antagonism
  • Drug Combinations
  • Drug Synergism
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / pharmacology*
  • Knee Joint / cytology
  • Matrix Metalloproteinase 13 / metabolism*
  • Platelet-Rich Plasma / chemistry*
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Blood Proteins
  • Drug Combinations
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • MMP13 protein, human
  • Matrix Metalloproteinase 13