title: 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.
authors.affiliation: Departments of Biochemistry, Rush University Medical Center, Chicago, IL, 60612.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Kc
authors.affiliation: Departments of Biochemistry, Rush University Medical Center, Chicago, IL, 60612.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, 60612.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Forsyth
authors.affiliation: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, 60612.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Voigt
authors.affiliation: Center for Sleep and Circadian Biology, Department of Neurobiology, Northwestern University, Evanston, IL, 60208.
authors.forename: Keith C
authors.initials: KC
authors.lastname: Summa
authors.affiliation: Center for Sleep and Circadian Biology, Department of Neurobiology, Northwestern University, Evanston, IL, 60208.
authors.forename: Martha Hotz
authors.initials: MH
authors.lastname: Vitaterna
authors.affiliation: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, 60612.
authors.forename: Beata
authors.initials: B
authors.lastname: Tryniszewska
authors.affiliation: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, 60612.|Departments of Pharmacology, Rush University Medical Center, Chicago, IL, 60612.|Departments of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL, 60612.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Netherlands.
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
authors.affiliation: Center for Sleep and Circadian Biology, Department of Neurobiology, Northwestern University, Evanston, IL, 60208.
authors.forename: Fred W
authors.initials: FW
authors.lastname: Turek
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom, M13 9PT.
authors.forename: Qing-Jun
authors.initials: QJ
authors.lastname: Meng
authors.affiliation: Departments of Biochemistry, Rush University Medical Center, Chicago, IL, 60612.|Departments of Orthopaedic Surgery, Internal Medicine, Rush University Medical Center, Chicago, IL, 60612.|Sections of Rheumatology, Rush University Medical Center, Chicago, IL, 60612.|Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, 60612.|Jesse Brown Veterans Affairs Medical Center at Chicago, IL 60612, USA.
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Im
mesh_terms: D000818:Animals; D001835:Body Weight; D002940:Circadian Rhythm; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D004777:Environment; D006801:Humans; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000503:physiopathology; D020370:Osteoarthritis, Knee / Q000209:etiology* / Q000503:physiopathology; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D011509:Proteoglycans