title: The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc.
abstract: METHODS
  Basic science, biologic study.
  
  
  OBJECTIVE
  To determine the potential benefits of using resveratrol (RSV) for intervertebral disc (IVD) matrix repair and regeneration.
  
  
  BACKGROUND
  The phytoestrogen RSV is a natural compound found in various plants including grapes and red wines. RSV has been reported to provide a protective effect on articular cartilage in rabbit models for arthritis, but its effect on spine cartilage is unknown. METHODS.: We studied the effect of RSV on bovine IVD cartilage homeostasis by assessing MMP-13 (potent catabolic factor) production, proteoglycan (PG) accumulation and synthesis, and the interaction between RSV and known catabolic factors such as bFGF or IL-1. To understand the molecular mechanisms by which RSV modulates MMP-13 and PG production, we also investigated its downstream target regulatory molecules.
  
  
  RESULTS
  Stimulation of bovine disc cells cultured in monolayer with bFGF or IL-1 augmented the production of MMP-13 and ADAMTS-4 at the transcriptional level and this augmentation was blocked by RSV. Incubation of nucleus pulposus cells with RSV for 21 days significantly increased PG accumulation per cell in a dose-dependent manner, increased PG synthesis, rescued PG losses induced by catabolic reagents bFGF and IL-1, and promoted cell survival to levels seen after incubation with the anabolic protein BMP7 100 ng/mL. Protein-DNA interaction array results suggest that RSV effectively suppresses downstream target molecules of bFGF and IL-1 responsible for oxidative stress, proliferation, and apoptosis.
  
  
  CONCLUSIONS
  Resveratrol is a potent anabolic mediator of bovine IVD cartilage homeostasis, revealing its potential as a unique biologic treatment to slow the progression of IVD degeneration. These data suggests RSV may have considerable promise in the treatment of disc degeneration.
authors.affiliation: Department of Biochemistry, Section of Rheumatology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Frank M
authors.initials: FM
authors.lastname: Phillips
authors.forename: Howard S
authors.initials: HS
authors.lastname: An
authors.forename: Michael
authors.initials: M
authors.lastname: Ellman
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Thonar
authors.forename: William
authors.initials: W
authors.lastname: Wu
authors.forename: Daniel
authors.initials: D
authors.lastname: Park
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Im
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005638:Fruit; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006706:Homeostasis; D007375:Interleukin-1 / Q000378:metabolism; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D048789:Phytoestrogens / Q000494:pharmacology*; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D027843:Vitis
chemical_list: D007375:Interleukin-1; D061965:Matrix Metalloproteinase Inhibitors; D048789:Phytoestrogens; D011509:Proteoglycans; D013267:Stilbenes; D016222:Fibroblast Growth Factor 2; D051722:ADAM Proteins; D053509:Matrix Metalloproteinase 13; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; D000077185:Resveratrol