RRC ID 42672
著者 Hinoi E, Ueshima T, Hojo H, Iemata M, Takarada T, Yoneda Y.
タイトル Up-regulation of per mRNA expression by parathyroid hormone through a protein kinase A-CREB-dependent mechanism in chondrocytes.
ジャーナル J Biol Chem
Abstract In bone, clock genes are involved in the circadian oscillation of bone formation and extracellular matrix expression. However, to date little attention has been paid to circadian rhythm in association with expression of clock genes during chondrogenesis in cartilage. In this study, we investigated the functional expression of different clock genes by chondrocytes in the course of cartilage development. The mRNA expression of types I, II, and X collagens exhibited a 24-h rhythm with a peak at zeitgeber time 6, in addition to a 24-h rhythmicity of all the clock genes examined in mouse femurs in vivo. Marked expression of different clock genes was seen in both osteoblastic MC3T3-E1 and chondrogenic ATDC5 cells in vitro, whereas parathyroid hormone (PTH) transiently increased period 1 (per1) mRNA expression at 1 h in both cell lines. Similar increases were seen in the mRNA levels for both per1 and per2 in prehypertrophic chondrocytes in metatarsal organotypic cultures within 2 h of exposure to PTH. PTH significantly activated the mouse per1 (mper1) and mper2 promoters but not the mper3 promoter in a manner sensitive to both a protein kinase A inhibitor and deletion of the cAMP-responsive element sequence (CRE) in ATDC5 cells. In HEK293 cells, introduction of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (bmal1)/clock enhanced mouse type II collagen first intron reporter activity without affecting promoter activity, with reduction effected by either per1 or per2. These results suggest that PTH directly stimulates mper expression through a protein kinase A-CRE-binding protein signaling pathway for subsequent regulation of bmal1/clock-dependent extracellular matrix expression in cartilage.
巻・号 281(33)
ページ 23632-42
公開日 2006-8-18
DOI 10.1074/jbc.M512362200
PII S0021-9258(19)46401-6
PMID 16777848
MeSH Animals CLOCK Proteins Cell Cycle Proteins Cell Line Chondrocytes / enzymology Chondrocytes / metabolism* Circadian Rhythm / genetics Collagen Type II / genetics Collagen Type II / metabolism Cyclic AMP Response Element-Binding Protein / physiology* Cyclic AMP-Dependent Protein Kinase Type II Cyclic AMP-Dependent Protein Kinases / physiology* Male Metatarsal Bones / metabolism Mice Nuclear Proteins / biosynthesis Nuclear Proteins / genetics* Nuclear Proteins / physiology Organ Culture Techniques Parathyroid Hormone / physiology* Period Circadian Proteins RNA, Messenger / biosynthesis* Tibia / metabolism Trans-Activators / biosynthesis Trans-Activators / genetics Trans-Activators / physiology Transcription Factors / biosynthesis Transcription Factors / genetics* Transcription Factors / physiology Up-Regulation / physiology*
IF 4.238
引用数 46
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 ATDC5(RCB0565) MC3T3-E1(RCB1126)