-
Tytuł:
-
Clock knockdown attenuated reactive oxygen species-mediated senescence of chondrocytes through restoring autophagic flux.
-
Autorzy:
-
Zhong J; Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Wang B; Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Wu B; Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Shang J; Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Jiang N; Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Cui A; Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Chen Y; Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Xu X; Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China. Electronic address: .
Lu H; Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China. Electronic address: .
-
Źródło:
-
Life sciences [Life Sci] 2021 Mar 15; Vol. 269, pp. 119036. Date of Electronic Publication: 2021 Jan 12.
-
Typ publikacji:
-
Journal Article
-
Język:
-
English
-
Imprint Name(s):
-
Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
-
MeSH Terms:
-
Autophagy*
Cellular Senescence*
Arthritis, Experimental/*pathology
CLOCK Proteins/*antagonists & inhibitors
Chondrocytes/*pathology
Osteoarthritis/*pathology
Reactive Oxygen Species/*metabolism
Animals ; Apoptosis ; Arthritis, Experimental/metabolism ; CLOCK Proteins/metabolism ; Cartilage, Articular/metabolism ; Cartilage, Articular/pathology ; Cell Cycle ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chondrocytes/metabolism ; Circadian Clocks ; Disease Models, Animal ; Homeostasis ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Osteoarthritis/metabolism
-
Contributed Indexing:
-
Keywords: Autophagic flux; Circadian rhythm; Osteoarthritis; Reactive oxygen species; Senescence
-
Substance Nomenclature:
-
0 (Reactive Oxygen Species)
EC 2.3.1.48 (CLOCK Proteins)
-
Entry Date(s):
-
Date Created: 20210115 Date Completed: 20210226 Latest Revision: 20210226
-
Update Code:
-
20240105
-
DOI:
-
10.1016/j.lfs.2021.119036
-
PMID:
-
33450259
-
Aims: Articular cartilage degeneration has been recognized as the primary pathological change in osteoarthritis (OA). Mechanisms that govern the shift from cartilage homeostasis to OA remain unknown. Previous studies have reported that intrinsic circadian clock in chondrocytes could function to optimize cartilage repair/remodeling to optimum times of day, but little is known about its molecular mechanisms. This study attempted to investigate the potential role and mechanism of circadian gene Clock in OA pathology.
Materials and Methods: The expression of Clock in OA chondrocytes and cartilage was detected by qRT-PCR, western blot and immunohistochemistry. Temporal gene expression changes were analyzed using qRT-PCR in chondrocytes transfected with siClock following dexamethasone synchronization. In addition, the effect of Clock knockdown on senescent phenotypes and autophagic flux was evaluated in chondrocytes treated with siClock or siCntrl.
Key Findings: The expression of Clock was up-regulated in OA cartilage from humans and mouse models. Clock knockdown had no influence on rhythmic expression of the downstream genes in primary chondrocytes. We also found that Clock knockdown elevated antioxidant enzyme activities, diminished reactive oxygen species (ROS) production and attenuated senescence of chondrocytes via restoring autophagic flux.
Significance: Clock knockdown can attenuate ROS-mediated senescence of chondrocytes through restoring autophagic flux in non-circadian manner, providing a potential therapeutic target for OA.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
