Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway

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 o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiaopeng Song, Tianwen Ma, Hailong Hu, Mingchao Zhao, Hui Bai, Xinyu Wang, Lin Liu, Ting Li, Xuanbo Sheng, Xinyu Xu, Xinmin Zhang, Li Gao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	circadian rhythm disturbance osteoarthritis wnt/β-catenin signaling pathway cartilage rat Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/27759b4e7ab64c919523a208194845e0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:27759b4e7ab64c919523a208194845e0
record_format	dspace
spelling	oai:doaj.org-article:27759b4e7ab64c919523a208194845e02021-11-11T07:21:52ZChronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway1663-981210.3389/fphar.2021.760988https://doaj.org/article/27759b4e7ab64c919523a208194845e02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.760988/fullhttps://doaj.org/toc/1663-9812With 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/β-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/β-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 β-catenin increased significantly; BMAL1, Aggrecan, and COL2A1 decreased significantly in either LD-shifted cartilage or BMAL1-KD chondrocytes. The expression of β-catenin and p-GSK-3β elevated, while p-β-catenin and GSK-3β 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/β-catenin signaling pathway.Xiaopeng SongXiaopeng SongTianwen MaTianwen MaHailong HuMingchao ZhaoHui BaiXinyu WangLin LiuTing LiXuanbo ShengXinyu XuXinmin ZhangLi GaoLi GaoFrontiers Media S.A.articlecircadian rhythm disturbanceosteoarthritiswnt/β-catenin signaling pathwaycartilageratTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circadian rhythm disturbance osteoarthritis wnt/β-catenin signaling pathway cartilage rat Therapeutics. Pharmacology RM1-950
spellingShingle	circadian rhythm disturbance osteoarthritis wnt/β-catenin signaling pathway cartilage rat Therapeutics. Pharmacology RM1-950 Xiaopeng Song Xiaopeng Song Tianwen Ma Tianwen Ma Hailong Hu Mingchao Zhao Hui Bai Xinyu Wang Lin Liu Ting Li Xuanbo Sheng Xinyu Xu Xinmin Zhang Li Gao Li Gao Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway
description	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/β-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/β-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 β-catenin increased significantly; BMAL1, Aggrecan, and COL2A1 decreased significantly in either LD-shifted cartilage or BMAL1-KD chondrocytes. The expression of β-catenin and p-GSK-3β elevated, while p-β-catenin and GSK-3β 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/β-catenin signaling pathway.
format	article
author	Xiaopeng Song Xiaopeng Song Tianwen Ma Tianwen Ma Hailong Hu Mingchao Zhao Hui Bai Xinyu Wang Lin Liu Ting Li Xuanbo Sheng Xinyu Xu Xinmin Zhang Li Gao Li Gao
author_facet	Xiaopeng Song Xiaopeng Song Tianwen Ma Tianwen Ma Hailong Hu Mingchao Zhao Hui Bai Xinyu Wang Lin Liu Ting Li Xuanbo Sheng Xinyu Xu Xinmin Zhang Li Gao Li Gao
author_sort	Xiaopeng Song
title	Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway
title_short	Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway
title_full	Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway
title_fullStr	Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway
title_full_unstemmed	Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway
title_sort	chronic circadian rhythm disturbance accelerates knee cartilage degeneration in rats accompanied by the activation of the canonical wnt/β-catenin signaling pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/27759b4e7ab64c919523a208194845e0
work_keys_str_mv	AT xiaopengsong chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT xiaopengsong chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT tianwenma chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT tianwenma chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT hailonghu chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT mingchaozhao chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT huibai chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT xinyuwang chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT linliu chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT tingli chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT xuanbosheng chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT xinyuxu chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT xinminzhang chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT ligao chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway AT ligao chroniccircadianrhythmdisturbanceaccelerateskneecartilagedegenerationinratsaccompaniedbytheactivationofthecanonicalwntbcateninsignalingpathway
_version_	1718439383128866816

Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway

Ejemplares similares