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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.

Original publication

DOI

10.3109/07420528.2016.1158183

Type

Journal article

Journal

Chronobiology international

Publication Date

01/2016

Volume

33

Pages

574 - 579

Addresses

a Botnar Research Centre , University of Oxford , Oxford , United Kingdom.

Keywords

Cells, Cultured, Chondrocytes, Humans, Osteoarthritis, Cell Differentiation, Circadian Rhythm, Aged, Aged, 80 and over, Middle Aged, Female, Male, Period Circadian Proteins, Circadian Clocks