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Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet

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posted on 09.05.2016, 00:00 by R Kc, X Li, CB Forsyth, RM Voigt, KC Summa, MH Vitaterna, B Tryniszewska, A Keshavarzian, FW Turek, QJ Meng, HJ Im
A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications.

Funding

This work was supported by NIH R01 grants AR062136 (to HJI), AA023417 (to AK), AA020216 (to AK/FWT), NIH R21 AR067935 (to HJI) and VA BLD&R Merit Award (to HJI).

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Publisher Statement

This is a copy of an article published in the Scientific Reports © 2015 Nature Publishing Group.

Publisher

Nature Publishing Group

issn

2045-2322

Issue date

20/11/2015

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