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首页> 外文期刊>Journal of Cellular Physiology >Environmental Disruption of Circadian Rhythm Predisposes Mice to Osteoarthritis-Like Changes in Knee Joint
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Environmental Disruption of Circadian Rhythm Predisposes Mice to Osteoarthritis-Like Changes in Knee Joint

机译：环境破坏的昼夜节律容易使老鼠Osteoarthritis-Like变化在膝关节

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Circadian rhythm dysfunction is linked to many diseases, yet pathophysiological roles in articular cartilage homeostasis and degenerative joint disease including osteoarthritis (OA) remains to be investigated in vivo. Here, we tested whether environmental or genetic disruption of circadian homeostasis predisposes to OA-like pathological changes. Male mice were examined for circadian locomotor activity upon changes in the light:dark (LD) cycle or genetic disruption of circadian rhythms. Wild-type (WT) mice were maintained on a constant 12h:12h LD cycle (12:12 LD) or exposed to weekly 12h phase shifts. Alternatively, male circadian mutant mice (Clock(19) or Csnk1e(tau) mutants) were compared with age-matched WT littermates that were maintained on a constant 12:12 LD cycle. Disruption of circadian rhythms promoted osteoarthritic changes by suppressing proteoglycan accumulation, upregulating matrix-degrading enzymes and downregulating anabolic mediators in the mouse knee joint. Mechanistically, these effects involved activation of the PKC-ERK-RUNX2/NFB and -catenin signaling pathways, stimulation of MMP-13 and ADAMTS-5, as well as suppression of the anabolic mediators SOX9 and TIMP-3 in articular chondrocytes of phase-shifted mice. Genetic disruption of circadian homeostasis does not predispose to OA-like pathological changes in joints. Our results, for the first time, provide compelling in vivo evidence that environmental disruption of circadian rhythms is a risk factor for the development of OA-like pathological changes in the mouse knee joint. J. Cell. Physiol. 230: 2174-2183, 2015. (c) 2015 Wiley Periodicals, Inc.
机译：昼夜节律紊乱与许多疾病,但病理生理作用关节软骨内稳态和退化关节疾病包括骨关节炎(OA)体内还有待调查。测试是否环境或遗传昼夜内稳态诱发的中断OA-like病变。检查生理运动活动光的变化:深色(LD)周期或基因昼夜节律的影响。老鼠维持在一个恒定的12 h: 12 h LD周期(十二12 LD)或暴露于每周12 h阶段转变。(时钟(19)或Csnk1e(τ)突变体)进行了比较与同龄WT同窝出生的保持在一个恒定的身子LD周期。提升的昼夜节律的中断骨关节炎的变化通过抑制蛋白多糖积累,移植基质降解酶和表达下调合成介质在鼠标膝关节。从力学上看,这些影响的激活PKC-ERK-RUNX2 /负反馈和连环蛋白MMP-13和信号通路,刺激ADAMTS-5以及合成代谢的抑制介质SOX9 TIMP-3关节软骨细胞相移的老鼠。昼夜内稳态不中断使OA-like病变关节。引人注目的体内环境的证据昼夜节律中断是一个风险因素OA-like病态的发展改变鼠标膝关节。杂志。230:2174 - 2183年,2015年。期刊、公司。

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