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J Biochem. 2013 Oct;154(4):373-81. doi: 10.1093/jb/mvt068. Epub 2013 Aug 11.

Different circadian expression of major matrix-related genes in various types of cartilage: modulation by light-dark conditions.

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Department of Dental and Medical Biochemistry, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8553; Laboratory for Systems Biology, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047; Department of Prosthetic Dentistry, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588; and Molecular Medicine Laboratories, Institute for Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan.


We screened circadian-regulated genes in rat cartilage by using a DNA microarray analysis. In rib growth-plate cartilage, numerous genes showed statistically significant circadian mRNA expression under both 12:12 h light-dark and constant darkness conditions. Type II collagen and aggrecan genes--along with several genes essential for post-translational modifications of collagen and aggrecan, including prolyl 4-hydroxylase 1, lysyl oxidase, lysyl oxidase-like 2 and 3'-phosphoadenosine 5'-phosphosulphate synthase 2--showed the same circadian phase. In addition, the mRNA level of SOX9, a master transcription factor for the synthesis of type II collagen and aggrecan, has a similar phase of circadian rhythms. The circadian expression of the matrix-related genes may be critical in the development and the growth of various cartilages, because similar circadian expression of the matrix-related genes was observed in hip joint cartilage. However, the circadian phase of the major matrix-related genes in the rib permanent cartilage was almost the converse of that in the rib growth-plate cartilage under light-dark conditions. We also found that half of the oscillating genes had conserved clock-regulatory elements, indicating contribution of the elements to the clock outputs. These findings suggest that the synthesis of the cartilage matrix macromolecules is controlled by cell-autonomous clocks depending upon the in vivo location of cartilage.


cartilage; circadian rhythm; clock; gene expression

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