A low ratio of n-6/n-3 polyunsaturated fatty acids suppresses matrix metalloproteinase 13 expression and reduces adjuvant-induced arthritis in rats.

Abstract

Increased expression of matrix metalloproteinase 13 (MMP13) in chondrocytes contributes to the development of osteoarthritis. The hypothesis of this study was that diet with a low ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced MMP13 expression in inflammatory chondrocytes in vitro and in vivo. Human chondrocytes were cultured with different ratios of linoleic acid (LA, n-6 PUFA) to α-linolenic acid (n-3 PUFA) from 1:1 to 10:1. Proliferation of chondrocytes, MMP13 protein and mRNA levels were detected, respectively. Sprague-Dawley rats (n=30) were fed diets containing different ratios of n-6/n-3 PUFA. Freund's complete adjuvant was injected to make the model of arthritis. Paw swelling rate was measured and all rats were euthanized after 6 weeks of treatment. Serum MMP13 and IL-1 were measured by enzyme-linked immunosorbent assay. Joint histological sections were stained with safranin-O Fast Green to evaluate cartilage damage. Low ratio of LA/α-linolenic acid decreased the mRNA and protein levels of MMP13 but did not affect chondrocytes proliferation. Ratios of PUFA such as 1:1 and 2:1 significantly reduced paw swelling rate, and serum MMP13 and IL-1 levels in a rat model. Histological staining showed that ratios of 1:1 and 2:1 PUFA significantly alleviated cartilage damage in adjuvant-induced arthritis. A ratio of n-6/n-3 PUFA of 1:1 showed the strongest inhibitory effect on MMP13. Our results indicate that a low ratio of n-6/n-3 PUFA at 1:1 significantly suppressed MMP13 expression both in vitro and in vivo and reduced adjuvant-induced arthritis in rats could be a means to control and reduce the symptoms of osteoarthritis.

• Authors: Haomiao Yu, Yadong Li, Lifeng Ma, Hai Meng, Xiaodong Bai, Zihan Fan, Fei Yu, Ai Guo
• Journal: Nutrition research (New York, N.Y.) (Nutr Res) Vol. 35 Issue 12 Pg. 1113-21 (Dec 2015) ISSN: 1879-0739 [Electronic] United States
• PMID: 26675329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-1
• RNA, Messenger
• alpha-Linolenic Acid
• Linoleic Acid
• Matrix Metalloproteinase 13

Topics

• Animals
• Arthritis, Experimental (blood, diet therapy, genetics, pathology)
• Cartilage (drug effects, pathology)
• Cartilage Diseases (blood, diet therapy, genetics, pathology)
• Chondrocytes (drug effects)
• Edema
• Humans
• Interleukin-1 (blood)
• Joints (drug effects, pathology)
• Linoleic Acid (administration & dosage, pharmacology)
• Male
• Matrix Metalloproteinase 13 (blood, genetics)
• Osteoarthritis (blood, diet therapy, genetics, pathology)
• RNA, Messenger (metabolism)
• Rats, Sprague-Dawley
• alpha-Linolenic Acid (administration & dosage, pharmacology)