title: AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice.
abstract: Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice. Furthermore, male but not female AMPKα cDKO mice exhibited severely spontaneous ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from AMPKα cDKO mice resulted in an enhanced interleukin-1β (IL-1β)-stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-κB (phospho-NF-κB) p65 and increased levels of apoptotic markers were detected in the cartilage of AMPKα cDKO mice compared with their WT littermates in vivo. Thus, our findings suggest that AMPK activity in chondrocytes is important in maintaining joint homeostasis and OA development.
authors.affiliation: Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, P.R. China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, P.R. China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Lu
authors.affiliation: Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, Jiangsu, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, Jiangsu, China.
authors.forename: Qiting
authors.initials: Q
authors.lastname: Ge
authors.affiliation: Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, P.R. China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, P.R. China.
authors.forename: Dongquan
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Huangxian
authors.initials: H
authors.lastname: Ju
authors.affiliation: Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, Jiangsu, China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Qin
authors.affiliation: Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, Jiangsu, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, Jiangsu, China.
authors.forename: Huajian
authors.initials: H
authors.lastname: Teng
authors.affiliation: Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, P.R. China.|Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, Jiangsu, China.|State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000375:Aging / Q000473:pathology*; D000818:Animals; D019902:Chondrocytes / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000473:pathology*; D011494:Protein Kinases / Q000172:deficiency*
chemical_list: D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases