title: Docosahexenoic acid treatment ameliorates cartilage degeneration via a p38 MAPK-dependent mechanism.
abstract: Osteoarthritis (OA) is a common chronic inflammatory disease, characterized by cartilage degradation. The aberrant expression of matrix metalloproteinase-13 (MMP-13) plays a vital role in the pathogenesis of OA. The anti‑inflammatory property of docosahexenoic acid (DHA) was previously revealed and showed that DHA retards the progress of many types of inflammatory disease. To evaluate the prophylactic function of DHA in OA, the effect of DHA on cartilage degeneration was assessed in interleukin‑1β (IL‑1β) stimulated human chondrosarcoma SW1353 cells or a rat model of adjuvant‑induced arthritis (AIA). The safe concentration range (0‑50 µg/ml in vitro) of DHA was determined by flow cytometry and MTT assay. The inhibitory effects of DHA on MMP‑13 mRNA and protein expression were confirmed by RT‑qPCR, ELISA and western blotting. Furthermore, findings of an in vivo study showed that DHA can increase the thickness of articular cartilage and decrease MMP‑13 expression in cartilage matrix in a rat AIA model. We also revealed the mechanism by which DHA ameliorates cartilage degeneration from OA. The DHA-mediated inhibition of MMP‑13 expression was partially attributed to the inactivation of the p38 mitogen‑activated protein kinases pathway by suppressing p‑p38 in IL-1β-stimulated SW1353 cells and a rat AIA model. Our findings suggested that DHA is a promising therapeutic agent that may be used for the prevention and treatment of OA.
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Ai
authors.initials: A
authors.lastname: Guo
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Surgery, Medical Care Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Haomiao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Yinpeng
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005620:Freund's Adjuvant; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D004281:Docosahexaenoic Acids; D005620:Freund's Adjuvant; D048051:p38 Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat