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

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.

Dietary Fats and Osteoarthritis: Insights, Evidences, and New Horizons

“…In a recent study, increased activation of the protein kinase Cδ (PKCδ)‐ERK‐RUNX2/NFκB signaling pathways was found to be present in the articular chondrocytes of environmentally shifted mice [Kc et al, ]. Extension of this study compared the effects of high fat diet (HFD) versus normal diet (ND) on OA development and concluded that HFD increased the activation of the same signaling pathway [Kc et al, ].…”

The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration

“…[14][15][16][17][18] We have previously shown that environmental disruption of circadian rhythm in mice, when combined with high fat diet, leads to degeneration of the lumbar IVD tissue in mice. 19 More recently, changes in the expression of circadian clock genes have been identified in rat IVD tissues following passive smoking (a risk factor for LBP). 20 However, no studies have examined whether IVD cells express intrinsic circadian clocks, how these IVD clocks are regulated, what their targets are and whether genetic disruption to the IVD clock impact on tissue homeostasis and susceptibility to degeneration.…”

Timing metabolism in cartilage and bone: links between circadian clocks and tissue homeostasis

“…This reduction in the amplitude of circadian oscillations could impact on the regulation of downstream genes involved in cartilage metabolism. It has also been reported that long-term environmental disruption of light/dark cycles that mimics many years of rotating shift work or chronic jet lag promotes the development of an OA-like phenotype in murine knee cartilage (Kc et al 2015).…”