PMID- 28225087
OWN - NLM
STAT- MEDLINE
DCOM- 20181029
LR  - 20220410
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
DP  - 2017 Feb 22
TI  - AMPK deficiency in chondrocytes accelerated the progression of 
      instability-induced and ageing-associated osteoarthritis in adult mice.
PG  - 43245
LID - 10.1038/srep43245 [doi]
LID - 43245
AB  - 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 AMPKalpha1 conditional knockout (AMPKalpha1 cKO), AMPKalpha2 conditional 
      knockout (AMPKalpha2 cKO) and AMPKalpha1alpha2 conditional double knockout (AMPKalpha cDKO) mice, 
      we found that compared with wild-type (WT) littermates, mutant mice displayed 
      accelerated severity of surgically induced OA, especially AMPKalpha cDKO mice. 
      Furthermore, male but not female AMPKalpha cDKO mice exhibited severely spontaneous 
      ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from 
      AMPKalpha cDKO mice resulted in an enhanced interleukin-1beta (IL-1beta)-stimulated 
      catabolic response. In addition, upregulated expression of matrix 
      metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-kappaB (phospho-NF-kappaB) 
      p65 and increased levels of apoptotic markers were detected in the cartilage of 
      AMPKalpha 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.
FAU - Zhou, Sheng
AU  - Zhou S
AD  - 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.
FAU - Lu, Wanli
AU  - Lu W
AD  - 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.
FAU - Chen, Liang
AU  - Chen L
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, Jiangsu, China.
FAU - Ge, Qiting
AU  - Ge Q
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, Jiangsu, China.
FAU - Chen, Dongyang
AU  - Chen D
AD  - 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.
FAU - Xu, Zhihong
AU  - Xu Z
AD  - 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.
FAU - Shi, Dongquan
AU  - Shi D
AD  - 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.
FAU - Dai, Jin
AU  - Dai J
AD  - 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.
FAU - Li, Jianxin
AU  - Li J
AD  - State Key Laboratory of Analytical Chemistry for Life Science, Nanjing 
      University, Hankou Road, Nanjing 210093, Jiangsu, China.
FAU - Ju, Huangxian
AU  - Ju H
AD  - State Key Laboratory of Analytical Chemistry for Life Science, Nanjing 
      University, Hankou Road, Nanjing 210093, Jiangsu, China.
FAU - Cao, Yi
AU  - Cao Y
AD  - Collaborative Innovation Center of Advanced Microstructures, National Laboratory 
      of Solid State Microstructure and Department of Physics, Nanjing University, 
      Hankou Road, Nanjing 210093, Jiangsu, China.
FAU - Qin, Jinzhong
AU  - Qin J
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, Jiangsu, China.
FAU - Chen, Shuai
AU  - Chen S
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, Jiangsu, China.
FAU - Teng, Huajian
AU  - Teng H
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, Jiangsu, China.
FAU - Jiang, Qing
AU  - Jiang Q
AD  - 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.
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, Jiangsu, China.
AD  - State Key Laboratory of Analytical Chemistry for Life Science, Nanjing 
      University, Hankou Road, Nanjing 210093, Jiangsu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170222
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Aging/*pathology
MH  - Animals
MH  - Chondrocytes/*enzymology/*pathology
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Osteoarthritis/*pathology
MH  - Protein Kinases/*deficiency
PMC - PMC5320548
COIS- The authors declare no competing financial interests.
EDAT- 2017/02/23 06:00
MHDA- 2018/10/30 06:00
PMCR- 2017/02/22
CRDT- 2017/02/23 06:00
PHST- 2016/09/01 00:00 [received]
PHST- 2017/01/23 00:00 [accepted]
PHST- 2017/02/23 06:00 [entrez]
PHST- 2017/02/23 06:00 [pubmed]
PHST- 2018/10/30 06:00 [medline]
PHST- 2017/02/22 00:00 [pmc-release]
AID - srep43245 [pii]
AID - 10.1038/srep43245 [doi]
PST - epublish
SO  - Sci Rep. 2017 Feb 22;7:43245. doi: 10.1038/srep43245.