title: The chondrocyte-intrinsic circadian clock is disrupted in human osteoarthritis.
abstract: Peripheral clocks are essential for driving cell differentiation. In osteoarthritis, loss of the normal differentiated chondrocyte (cartilage cell) phenotype is causative of disease. We investigated whether clock gene expression differed in osteoarthritic compared to "healthy" chondrocytes and used RNAi to determine whether the differences observed could affect chondrocyte phenotype. Following serum shock, PER2 expression was significantly higher, whereas BMAL1 expression was significantly lower, in osteoarthritic chondrocytes. Knockdown of BMAL1 in "healthy" chondrocytes was associated with higher cell proliferation and MMP13 expression, features characteristic of the osteoarthritic chondrocyte phenotype. Chondrocyte-intrinsic clock disruption may be a critical early step in osteoarthritis development.
authors.affiliation: a Botnar Research Centre , University of Oxford , Oxford , United Kingdom.
authors.forename: Sarah J B
authors.initials: SJ
authors.lastname: Snelling
authors.affiliation: b Department of Orthopaedics , MidCentral District Health Board , Palmerston North , New Zealand.
authors.forename: Alana
authors.initials: A
authors.lastname: Forster
authors.affiliation: b Department of Orthopaedics , MidCentral District Health Board , Palmerston North , New Zealand.
authors.forename: Supratim
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: a Botnar Research Centre , University of Oxford , Oxford , United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Price
authors.affiliation: c College of Health , Massey University , Palmerston North , New Zealand.|d Faculty of Medical and Health Sciences , University of Auckland , Auckland , New Zealand .
authors.forename: Raewyn C
authors.initials: RC
authors.lastname: Poulsen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000503:physiopathology*; D056950:Period Circadian Proteins / Q000378:metabolism
chemical_list: C421902:PER2 protein, human; D056950:Period Circadian Proteins
keywords: Cartilage; cell phenotype; cell proliferation; matrix metalloproteinases; peripheral circadian clocks; peripheral clocks in disease