title: 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.affiliation: Department of Surgery, Medical Care Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Haomiao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Zihan
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China. Electronic address: guoaij@139.com.
authors.forename: Ai
authors.initials: A
authors.lastname: Guo
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology; D002357:Cartilage Diseases / Q000097:blood / Q000178:diet therapy / Q000235:genetics / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects; D004487:Edema; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D007596:Joints / Q000187:drug effects* / Q000473:pathology; D019787:Linoleic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000097:blood* / Q000235:genetics; D010003:Osteoarthritis / Q000097:blood / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017962:alpha-Linolenic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D017962:alpha-Linolenic Acid; D019787:Linoleic Acid; D053509:Matrix Metalloproteinase 13
keywords: Chondrocytes; Fatty acids; Matrix metalloproteinase 13; Osteoarthritis; Rat; Ratio of PUFA