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The Action of Resveratrol, a Phytoestrogen Found in Grapes, on the Intervertebral Disc

Li, Xin, MD, PhD*; Phillips, Frank M., MD; An, Howard S., MD; Ellman, Michael, MD*†; Thonar, Eugene J., PhD*†‡; Wu, William, PhD§; Park, Daniel, MD; Im, Hee-Jeong, PhD*†‡

doi: 10.1097/BRS.0b013e3181883883
Basic Science

Study Design. Basic science, biologic study.

Objective. To determine the potential benefits of using resveratrol (RSV) for intervertebral disc (IVD) matrix repair and regeneration.

Summary of Background Data. 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.

Conclusion. 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.

The phytoestrogen resveratrol (RSV) is a natural polyphenol compound found in various plants including grapes and red wines. Treatment of bovine disc cells with RSV inhibited MMP-13 expression at the transcriptional level, increased proteoglycan accumulation, and stimulated proteoglycan synthesis in bovine NP cells. In addition, RSV reversed the catabolic effects of bFGF and IL-1 that have been implicated in disc degeneration.

From the Departments of *Biochemistry, †Orthopedic Surgery, and ‡Internal Medicine, Section of Rheumatology, Rush University Medical Center, Chicago, IL; and §Bone & Joint Center, Henry Ford Hospital, Detroit, MI.

Acknowledgment date: February 19, 2008. First revision date: June 4, 2008. Second revision date: July 1, 2008. Acceptance date: July 7, 2008.

The manuscript submitted does not contain information about medical device(s)/drug(s).

Foundation (Arthritis Foundation and National Arthritis Research Foundation) funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

This work was funded by NIH RO1 AR053220 (to H.J.I.), NIH training grant 2T-AR-007590, Arthritis Foundation (to H.J.I.), National Arthritis Research Foundation (to H.J.I.), Rush University Committee on Research Funds (H.J.I.), and Falk Foundation and NIH AR48152 (to H.S.A.).

Address correspondence and reprint requests to Hee-Jeong Im, PhD, Department of Biochemistry, Rush University Medical Center, Cohn Research BD 516, 1735 W. Harrison, Chicago, IL 60612; E-mail:

© 2008 Lippincott Williams & Wilkins, Inc.