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

Overview

Journal Spine (Phila Pa 1976)

Specialty Orthopedics

Date 2008 Nov 18

PMID 19011540

Citations 42

Authors

Xin Li

Frank M Phillips

Howard S An

Michael Ellman

Eugene J Thonar

William Wu

Daniel Park

Hee-Jeong Im

Affiliations

Soon will be listed here.

Abstract

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.

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References

Fremont L . Biological effects of resveratrol. Life Sci. 2000; 66(8):663-73. DOI: 10.1016/s0024-3205(99)00410-5. View

Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K . Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986; 29(8):1039-49. DOI: 10.1002/art.1780290816. View

Raggatt L, Jefcoat Jr S, Choudhury I, Williams S, Tiku M, Partridge N . Matrix metalloproteinase-13 influences ERK signalling in articular rabbit chondrocytes. Osteoarthritis Cartilage. 2006; 14(7):680-9. DOI: 10.1016/j.joca.2006.01.006. View

Andersson G . Epidemiological features of chronic low-back pain. Lancet. 1999; 354(9178):581-5. DOI: 10.1016/S0140-6736(99)01312-4. View

Pendas A, Uria J, Jimenez M, Balbin M, Freije J, Lopez-Otin C . An overview of collagenase-3 expression in malignant tumors and analysis of its potential value as a target in antitumor therapies. Clin Chim Acta. 2000; 291(2):137-55. DOI: 10.1016/s0009-8981(99)00225-9. View

Im H, Pacione C, Chubinskaya S, van Wijnen A, Sun Y, Loeser R . Inhibitory effects of insulin-like growth factor-1 and osteogenic protein-1 on fibronectin fragment- and interleukin-1beta-stimulated matrix metalloproteinase-13 expression in human chondrocytes. J Biol Chem. 2003; 278(28):25386-94. PMC: 2895259. DOI: 10.1074/jbc.M302048200. View

Buckwalter J, Kuettner K, Thonar E . Age-related changes in articular cartilage proteoglycans: electron microscopic studies. J Orthop Res. 1985; 3(3):251-7. DOI: 10.1002/jor.1100030301. View

Shakibaei M, John T, Seifarth C, Mobasheri A . Resveratrol inhibits IL-1 beta-induced stimulation of caspase-3 and cleavage of PARP in human articular chondrocytes in vitro. Ann N Y Acad Sci. 2007; 1095:554-63. DOI: 10.1196/annals.1397.060. View

Le Maitre C, Hoyland J, Freemont A . Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile. Arthritis Res Ther. 2007; 9(4):R77. PMC: 2206382. DOI: 10.1186/ar2275. View

10.

Yammani R, Carlson C, Bresnick A, Loeser R . Increase in production of matrix metalloproteinase 13 by human articular chondrocytes due to stimulation with S100A4: Role of the receptor for advanced glycation end products. Arthritis Rheum. 2006; 54(9):2901-11. DOI: 10.1002/art.22042. View

11.

Jang M, Cai L, Udeani G, Slowing K, Thomas C, Beecher C . Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997; 275(5297):218-20. DOI: 10.1126/science.275.5297.218. View

12.

Martinez J, Moreno J . Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem Pharmacol. 2000; 59(7):865-70. DOI: 10.1016/s0006-2952(99)00380-9. View

13.

Haider U, Sorescu D, Griendling K, Vollmar A, Dirsch V . Resveratrol suppresses angiotensin II-induced Akt/protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells. Mol Pharmacol. 2002; 62(4):772-7. DOI: 10.1124/mol.62.4.772. View

14.

Huang K, Lin M, Cheng G . Anti-inflammatory tetramers of resveratrol from the roots of Vitis amurensis and the conformations of the seven-membered ring in some oligostilbenes. Phytochemistry. 2001; 58(2):357-62. DOI: 10.1016/s0031-9422(01)00224-2. View

15.

Shinmei M, Kikuchi T, Yamagishi M, Shimomura Y . The role of interleukin-1 on proteoglycan metabolism of rabbit annulus fibrosus cells cultured in vitro. Spine (Phila Pa 1976). 1988; 13(11):1284-90. DOI: 10.1097/00007632-198811000-00014. View

16.

Mooney V . The classification of low back pain. Ann Med. 1989; 21(5):321-5. DOI: 10.3109/07853898909149215. View

17.

Ignatowicz E, Baer-Dubowska W . Resveratrol, a natural chemopreventive agent against degenerative diseases. Pol J Pharmacol. 2002; 53(6):557-69. View

18.

Loeser R, Todd M, Seely B . Prolonged treatment of human osteoarthritic chondrocytes with insulin-like growth factor-I stimulates proteoglycan synthesis but not proteoglycan matrix accumulation in alginate cultures. J Rheumatol. 2003; 30(7):1565-70. View

19.

Gruber H, Hoelscher G, Leslie K, Ingram J, Hanley Jr E . Three-dimensional culture of human disc cells within agarose or a collagen sponge: assessment of proteoglycan production. Biomaterials. 2005; 27(3):371-6. DOI: 10.1016/j.biomaterials.2005.06.032. View

20.

An H, Thonar E, Masuda K . Biological repair of intervertebral disc. Spine (Phila Pa 1976). 2003; 28(15 Suppl):S86-92. DOI: 10.1097/01.BRS.0000076904.99434.40. View