Osteoarthritis (OA) is a common and debilitating joint disease which develops and progresses with age. Despite extensive research into the disease, potent disease-modifying drugs remain elusive. Changes to the character and function of chondrocytes of the articular cartilage underly the pathogenesis of OA. A recently emerging facet of chondrocyte biology that has been implicated in OA pathogenesis is the role of circadian rhythms, and the cellular clock which governs rhythmic gene transcription. Here, we review the role of the chondrocyte's cellular clock in governing normal homeostasis, and explore the wide range of consequences that contribute to OA development when the clock is dysregulated by aging and other factors. Finally, we explore how harnessing this understanding of clock mechanics in aging and OA can be translated into novel treatment strategies, or 'chronotherapies', for patients.
机构:
Hop Paul Brousse, Chronotherapy Unit, Med Oncol Serv, Villejuif, France
INSERM, Paris, France
European Org Res Treatment Canc, Chronotherapy Grp, Brussels, BelgiumHop Paul Brousse, Chronotherapy Unit, Med Oncol Serv, Villejuif, France
机构:
Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
Dudek, Michal
Meng, Qing-Jun
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Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
机构:
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst,Dept Neurol, Boston, MA 02114 USAHarvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst,Dept Neurol, Boston, MA 02114 USA
Videnovic, Aleksandar
Lazar, Alpar S.
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Univ Cambridge, John Geest Ctr Brain Repair, Dept Clin Neurosci, Cambridge CB2 2PY, EnglandHarvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst,Dept Neurol, Boston, MA 02114 USA
Lazar, Alpar S.
Barker, Roger A.
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Univ Cambridge, John Geest Ctr Brain Repair, Dept Clin Neurosci, Cambridge CB2 2PY, EnglandHarvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst,Dept Neurol, Boston, MA 02114 USA
Barker, Roger A.
Overeem, Sebastiaan
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Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6500 HB Nijmegen, NetherlandsHarvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst,Dept Neurol, Boston, MA 02114 USA