Abstract
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.
Highlights
A variety of environmental factors contribute to progressive development of osteoarthritis (OA)
We performed histological analyses to evaluate the effects of chronic circadian rhythm disruption and a high-fat diet (HFD) on the pathological changes in mouse knee joints
Histopathological grading was performed in the medial femoral condyle (MFC) and the medial tibial plateau (MTP)
Summary
A variety of environmental factors contribute to progressive development of osteoarthritis (OA). 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. Chronic environmental disruption of circadian rhythms predisposes mice to pathological changes in the knee joint as reflected by proteoglycan (PG) loss, fibrillation, upregulation of matrix-degrading enzyme production, and concomitant downregulation of chondrogenic factors. Recent studies have demonstrated that a high-fat diet (HFD) can adversely affect circadian rhythms and alter the expression of clock-controlled genes involved in energy homeostasis in mice[11]. In an effort to better understand the adverse effect of chronic circadian rhythm disruption on OA, in the present study we investigated how HFD interacts with the circadian rhythm disruption protocol to aggravate OA progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
