title: Explore the variation of MMP3, JNK, p38 MAPKs, and autophagy at the early stage of osteoarthritis.
abstract: Osteoarthritis is a chronic disease characterized by cartilage degeneration and chondrocyte apoptosis. Mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in regulating OA process. Autophagy has an important effect on the OA process, and it is believed to be regulated by MAPKs. To reveal the mechanism and the effect of JNK and p38 MAPKs on matrix metalloproteinase 3 (MMP3) and autophagy in OA, the study established OA model in rabbits, used the measurement of the Osteoarthritis Research Society International scoring system to evaluate OA model, and conducted general observation, histological observation, and Western blotting of JNK, phosphorylate-JNK (P-JNK), p38, phosphorylate-p38 (P-p38), MMP3, and light-chain 3 (LC3)-II/LC3-I to explore the variation of JNK, p38 MAPKs, and autophagy at the early stage of OA. With OA progressing at the early stage, MMP3, P-p38, and P-JNK were gradually upregulated from the baseline to the peak in study groups when compared with the control group; JNK and p38 variated of turbulence without statistical difference; and LC3-II/LC3-I had a decreasing tendency from the 0- to 15-day group. This study identifies that compromised autophagy may be related to the OA progress and that JNK and p38 MAPKs have positive regulation on MMP3 and negative regulation on autophagy. It also implicates a new therapeutic strategy for OA and other degenerate diseases based on selective MAPK inhibitors, reduction of MMP3, and autophagy.
authors.affiliation: Department of Rehabilitation Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Rehabilitation Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Changjie
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Department of Rehabilitation Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Chunna
authors.initials: C
authors.lastname: Lan
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D006651:Histocytochemistry; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011817:Rabbits; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D019278:Matrix Metalloproteinase 3
keywords: JNK; LC3; MAPK; autophagy; osteoarthritis; p38; signaling pathway