PMID- 34858186
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211204
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in 
      Rats Accompanied by the Activation of the Canonical Wnt/beta-Catenin Signaling 
      Pathway.
PG  - 760988
LID - 10.3389/fphar.2021.760988 [doi]
LID - 760988
AB  - With the gradual deepening of understanding of systemic health and quality of 
      life, the factors affecting osteoarthritis (OA) are not limited to mechanical 
      injury, metabolic abnormality, age and obesity, etc., but circadian rhythm, which 
      plays a non-negligible role in human daily life. The purpose of this study was to 
      explore the molecular mechanism of chronic circadian rhythm disturbance (CRD) 
      inducing cartilage OA-like degeneration. Rats with the anterior cruciate ligament 
      excision transection (ACLT) were used to establish the early-stage OA model 
      (6-week). The light/dark (LD) cycle shifted 12 h per week for 22 weeks in order 
      to establish a chronic CRD model. BMAL1 knockdown (KD) and Wnt/beta-catenin pathway 
      inhibition were performed in chondrocytes. The contents of proinflammatory 
      factors and OA biomarkers in serum and chondrocyte secretions were detected by 
      ELISA. Pathological and immunohistochemical staining of articular cartilage 
      indicated the deterioration of cartilage. WB and qPCR were used to evaluate the 
      relationship between matrix degradation and the activation of Wnt/beta-catenin 
      signaling pathway in chondrocytes. We found that chronic CRD could cause OA-like 
      pathological changes in knee cartilage of rats, accelerating cartilage matrix 
      degradation and synovial inflammation. The expression of MMP-3, MMP-13, ADAMTS-4, 
      and beta-catenin increased significantly; BMAL1, Aggrecan, and COL2A1 decreased 
      significantly in either LD-shifted cartilage or BMAL1-KD chondrocytes. The 
      expression of beta-catenin and p-GSK-3beta elevated, while p-beta-catenin and GSK-3beta 
      diminished. The inhibitor XAV-939 was able to mitigated the increased 
      inflammation produced by transfected siBMAL1. Our study demonstrates that chronic 
      CRD disrupts the balance of matrix synthesis and catabolic metabolism in 
      cartilage and chondrocytes, and it is related to the activation of the canonical 
      Wnt/beta-catenin signaling pathway.
CI  - Copyright (c) 2021 Song, Ma, Hu, Zhao, Bai, Wang, Liu, Li, Sheng, Xu, Zhang and 
      Gao.
FAU - Song, Xiaopeng
AU  - Song X
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agriculture University, Harbin, China.
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Ma, Tianwen
AU  - Ma T
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agriculture University, Harbin, China.
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Hu, Hailong
AU  - Hu H
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Zhao, Mingchao
AU  - Zhao M
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Bai, Hui
AU  - Bai H
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Wang, Xinyu
AU  - Wang X
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Liu, Lin
AU  - Liu L
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Li, Ting
AU  - Li T
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Sheng, Xuanbo
AU  - Sheng X
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Xu, Xinyu
AU  - Xu X
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Zhang, Xinmin
AU  - Zhang X
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Gao, Li
AU  - Gao L
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agriculture University, Harbin, China.
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
LA  - eng
PT  - Journal Article
DEP - 20211111
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8632052
OTO - NOTNLM
OT  - cartilage
OT  - circadian rhythm disturbance
OT  - osteoarthritis
OT  - rat
OT  - wnt/beta-catenin signaling pathway
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/12/04 06:00
MHDA- 2021/12/04 06:01
PMCR- 2021/11/11
CRDT- 2021/12/03 07:01
PHST- 2021/08/19 00:00 [received]
PHST- 2021/10/11 00:00 [accepted]
PHST- 2021/12/03 07:01 [entrez]
PHST- 2021/12/04 06:00 [pubmed]
PHST- 2021/12/04 06:01 [medline]
PHST- 2021/11/11 00:00 [pmc-release]
AID - 760988 [pii]
AID - 10.3389/fphar.2021.760988 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Nov 11;12:760988. doi: 10.3389/fphar.2021.760988. 
      eCollection 2021.