Per1

A Negative Correlation Between Per1 and Sox6 Expression During Chondrogenic Differentiation in Pre-chondrocytic ATDC5 Cells.

"Pre-chondrocytes undergo cellular differentiation stages during chondrogenesis under the influence by different transcription factors such as sry-type high mobility group box-9 (Sox9) and runt-related transcription factor-2 (Runx2). We have shown upregulation by parathyroid hormone (PTH) of the clock gene Period-1 (Per1) through the cAMP/protein kinase A signaling pathway in pre-chondrocytic ATDC5 cells. Here, we investigated the role of Per1 in the suppression of chondrogenic differentiation by PTH. In ATDC5 cells exposed to 10 nM PTH, a drastic but transient increase in Per1 expression was seen only 1 h after addition together with a prolonged decrease in Sox6 levels. However, no significant changes were induced in Sox5 and Runx2 levels in cells exposed to PTH. In stable Per1 transfectants, a significant decrease in Sox6 levels was seen, with no significant changes in Sox5 and Sox9 levels, in addition to the inhibition of gene transactivation by Sox9 allies. Knockdown of Per1 by siRNA significantly increased the Sox6 and type II collagen levels in cells cultured for 24 - 60 h. Per1 plays a role in the suppressed chondrocytic differentiation by PTH through a mechanism relevant to negative regulation of transactivation of the Sox6 gene during chondrogenesis."

"2.2 kb of the 5′ flanking region of the mouse Sox6 gene contains one putative E-box (CACGTG), which is a target element recognized by the master clock molecules Bmal1/Clock heterodimer"

It seems that Sox9 levels were enhanced by Per1 but ColII levels were still way down.

"downregulation of Sox6 would lead to suppression of the gene transactivation mediated by the Sox9 trimeric complex upstream of the Col II gene whose translation is essential for chondrogenesis in ATDC5 cells."