The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc.
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.
Li
Xin
X
Department of Biochemistry, Section of Rheumatology, Rush University Medical Center, Chicago, IL 60612, USA.
Phillips
Frank M
FM
An
Howard S
HS
Ellman
Michael
M
Thonar
Eugene J
EJ
Wu
William
W
Park
Daniel
D
Im
Hee-Jeong
HJ
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
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