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.

KEYWORDS:

• Cartilage
• cell phenotype
• cell proliferation
• peripheral circadian clocks
• peripheral clocks in disease
• matrix metalloproteinases

Declaration of interest

All authors declare no conflict of interest. This study was funded by the Palmerston North Medical Research Foundation, Arthritis Research UK (20087) and the NIHR Oxford Musculoskeletal Biomedical Research Unit.