Details

Autor(en) / Beteiligte

• Kc, Ranjan
• Li, Xin
• Voigt, Robin M.
• Ellman, Michael B.
• Summa, Keith C.
• Vitaterna, Martha Hotz
• Keshavarizian, Ali
• Turek, Fred W.
• Meng, Qing-Jun
• Stein, Gary S.
• van Wijnen, Andre J.
• Chen, Di
• Forsyth, Christopher B.
• Im, Hee-Jeong

Titel

Environmental Disruption of Circadian Rhythm Predisposes Mice to Osteoarthritis-Like Changes in Knee Joint

Ist Teil von

• Journal of cellular physiology, 2015-09, Vol.230 (9), p.2174-2183

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2015

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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 12 h:12 h LD cycle (12:12 LD) or exposed to weekly 12 h phase shifts. Alternatively, male circadian mutant mice (ClockΔ19 or Csnk1etau 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 PKCδ‐ERK‐RUNX2/NFκB and β‐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. © 2015 Wiley Periodicals, Inc.