title: Negative correlation between Per1 and Sox6 expression during chondrogenic differentiation in pre-chondrocytic ATDC5 cells.
abstract: 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. These results suggest that 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.
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School, Kanazawa, Ishikawa 920-1192, Japan.
authors.forename: Nguyen Quynh
authors.initials: NQ
authors.lastname: Le
authors.forename: Nguyen Thanh
authors.initials: NT
authors.lastname: Binh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takarada
authors.forename: Mika
authors.initials: M
authors.lastname: Takarada-Iemata
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hinoi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering; D055755:SOXD Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D010281:Parathyroid Hormone; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D034741:RNA, Small Interfering; D055755:SOXD Transcription Factors; C095939:Sox6 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases