PMID- 26873249 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20161230 IS - 1521-6551 (Electronic) IS - 1521-6543 (Linking) VI - 68 IP - 4 DP - 2016 Apr TI - Explore the variation of MMP3, JNK, p38 MAPKs, and autophagy at the early stage of osteoarthritis. PG - 293-302 LID - 10.1002/iub.1482 [doi] AB - 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. CI - (c) 2016 International Union of Biochemistry and Molecular Biology. FAU - Shi, Jie AU - Shi J AD - Department of Rehabilitation Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China. FAU - Zhang, Changjie AU - Zhang C AD - Department of Rehabilitation Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China. FAU - Yi, Zhongjie AU - Yi Z AD - Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China. FAU - Lan, Chunna AU - Lan C AD - Department of Rehabilitation Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China. LA - eng PT - Journal Article DEP - 20160213 PL - England TA - IUBMB Life JT - IUBMB life JID - 100888706 RN - 0 (Microtubule-Associated Proteins) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Autophagy/*genetics MH - Cartilage, Articular/metabolism/pathology MH - Chondrocytes/*metabolism/pathology MH - Disease Models, Animal MH - Disease Progression MH - Gene Expression Regulation MH - Histocytochemistry MH - Humans MH - MAP Kinase Kinase 4/*genetics/metabolism MH - Male MH - Matrix Metalloproteinase 3/*genetics/metabolism MH - Microtubule-Associated Proteins/genetics/metabolism MH - Osteoarthritis/*genetics/metabolism/pathology MH - Phosphorylation MH - Rabbits MH - Signal Transduction MH - p38 Mitogen-Activated Protein Kinases/*genetics/metabolism OTO - NOTNLM OT - JNK OT - LC3 OT - MAPK OT - autophagy OT - osteoarthritis OT - p38 OT - signaling pathway EDAT- 2016/02/14 06:00 MHDA- 2016/12/15 06:00 CRDT- 2016/02/14 06:00 PHST- 2015/12/12 00:00 [received] PHST- 2016/01/17 00:00 [accepted] PHST- 2016/02/14 06:00 [entrez] PHST- 2016/02/14 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - 10.1002/iub.1482 [doi] PST - ppublish SO - IUBMB Life. 2016 Apr;68(4):293-302. doi: 10.1002/iub.1482. Epub 2016 Feb 13.