Per-1 is a specific clock gene regulated by parathyroid hormone (PTH) signaling in osteoblasts and is functional for the transcriptional events induced by PTH.
Per-1 is one of the clock genes and is known to regulate various biological events including bone mass determination. Parathyroid hormone is anabolic to bone while the mechanism of its action is not fully understood. Here, we examined the role of PTH on Per-1 gene expression under osteoblast specific PTH signaling. Constitutively active PTH receptor (caPPR) expressed specifically in osteoblasts in transgenic mice activates Per-1 gene expression in bone. This is specific as expression of other clock gene Bmal-1 is not affected by caPPR over-expression. Per-1 is also expressed in osteoblastic cell line. Interestingly, Per-1 expression is required for PTH signaling-induced CRE dependent transcription. This is forming a positive feed back loop in the anabolic action of PTH signaling and Per-1 in bone. These data indicate that PTH singling in osteoblasts activates Per-1 gene expression in vivo in association with its anabolic action in bone at least in part through the regulation of transcriptional events.
Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, Bunkyo-Ku, Tokyo, Japan.
Ryo
R
Hanyu
Tadayoshi
T
Hayata
Masashi
M
Nagao
Yoshitomo
Y
Saita
Hiroaki
H
Hemmi
Takuya
T
Notomi
Tetsuya
T
Nakamoto
Ernestina
E
Schipani
Henry
H
Knonenbery
Kazuo
K
Kaneko
Hisashi
H
Kurosawa
Yoichi
Y
Ezura
Masaki
M
Noda
D056930:ARNTL Transcription Factors / Q000235:genetics; D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000235:genetics; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography
D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D010281:Parathyroid Hormone; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D044168:Receptor, Parathyroid Hormone, Type 1