PMID- 34895043
OWN - NLM
STAT- MEDLINE
DCOM- 20220215
LR  - 20220215
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 12
IP  - 2
DP  - 2021 Dec
TI  - Celecoxib prevents tumor necrosis factor-alpha (TNF-alpha)-induced cellular senescence in 
      human chondrocytes.
PG  - 12812-12820
LID - 10.1080/21655979.2021.2003661 [doi]
AB  - Osteoarthritis (OA) is a cartilage degenerative disease commonly observed in the 
      elderly population and significantly impacts the normal life of OA patients. It 
      has been reported that the development of pathological cell senescence in 
      chondrocytes is involved in the pathogenesis of OA. Celecoxib is a common 
      non-steroidal anti-inflammatory drug, and it has been recently reported to exert 
      therapeutic effects on OA. However, its underlying mechanism is still unclear. 
      The present study intends to explore its mechanism and provide fundamental 
      evidence for the application of Celecoxib in the treatment of clinical OA. Tumor 
      necrosis factor-alpha (TNF-alpha) was utilized to establish an in vitro model of 
      chondrocytes senescence. The elevated reactive oxygen species (ROS) generation, 
      increased cell cycle arrest in G0/G1 phase, reduced telomerase activity, and 
      upregulated senescence-associatedbeta-galactosidase (SA-beta-Gal) staining were all 
      observed in TNF-alpha-treated chondrocytes, which were then dramatically reversed by 
      10 and 20 muM Celecoxib. In addition, the upregulated DNA damage biomarkers, 
      p-ATM, and p-CHK2, observed in TNF-alpha-treated chondrocytes were significantly 
      downregulated by 10 and 20 muM Celecoxib. Lastly, the expression level of p21 and 
      p53 was greatly elevated in chondrocytes by stimulation with TNF-alpha which was then 
      pronouncedly repressed by treatment with Celecoxib. Taken together, our data 
      reveal that Celecoxib ameliorated TNF-alpha-induced cellular senescence in human 
      chondrocytes.
FAU - Wang, Qunli
AU  - Wang Q
AD  - Department of Orthopaedic Center, Affiliated Haikou Hospital of Xiangya Medical 
      College, Central South University, Haikou, Hainan, China.
FAU - Chen, Qi
AU  - Chen Q
AD  - Department of Orthopedics, The 928th Hospital of the Joint Logistic Support Force 
      of the People's Liberation Army, Haikou, Hainan, China.
FAU - Sui, Jie
AU  - Sui J
AUID- ORCID: 0000-0001-9720-8614
AD  - Department of Orthopedics, The 904th Hospital of the Joint Logistic Support Force 
      of the People's Liberation Army, Changzhou, Jiangsu, China.
FAU - Tu, Yuanyuan
AU  - Tu Y
AD  - Department of Orthopaedic Center, Affiliated Haikou Hospital of Xiangya Medical 
      College, Central South University, Haikou, Hainan, China.
FAU - Guo, Xiang
AU  - Guo X
AD  - Department of Orthopaedic Center, Affiliated Haikou Hospital of Xiangya Medical 
      College, Central South University, Haikou, Hainan, China.
FAU - Li, Feng
AU  - Li F
AD  - Department of Orthopedics, The 928th Hospital of the Joint Logistic Support Force 
      of the People's Liberation Army, Haikou, Hainan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.1.11 (Checkpoint Kinase 2)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (CHEK2 protein, human)
RN  - EC 2.7.7.49 (Telomerase)
RN  - JCX84Q7J1L (Celecoxib)
SB  - IM
MH  - Ataxia Telangiectasia Mutated Proteins/metabolism
MH  - Celecoxib/chemistry/*pharmacology
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Death/drug effects
MH  - Cell Line
MH  - Cellular Senescence/*drug effects
MH  - Checkpoint Kinase 2/metabolism
MH  - Chondrocytes/drug effects/metabolism/*pathology
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - G1 Phase/drug effects
MH  - Humans
MH  - Phosphorylation/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Resting Phase, Cell Cycle/drug effects
MH  - Telomerase/metabolism
MH  - Tumor Necrosis Factor-alpha/*toxicity
MH  - Tumor Suppressor Protein p53/metabolism
PMC - PMC8809908
OTO - NOTNLM
OT  - Celecoxib
OT  - cell senescence
OT  - chondrocytes
OT  - osteoarthritis
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2021/12/14 06:00
MHDA- 2022/02/16 06:00
PMCR- 2021/12/13
CRDT- 2021/12/13 11:31
PHST- 2021/12/13 11:31 [entrez]
PHST- 2021/12/14 06:00 [pubmed]
PHST- 2022/02/16 06:00 [medline]
PHST- 2021/12/13 00:00 [pmc-release]
AID - 2003661 [pii]
AID - 10.1080/21655979.2021.2003661 [doi]
PST - ppublish
SO  - Bioengineered. 2021 Dec;12(2):12812-12820. doi: 10.1080/21655979.2021.2003661.