Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, Bunkyo-Ku, Tokyo, Japan.
J Cell Biochem. 2011 Feb;112(2):433-8. doi: 10.1002/jcb.22957.
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.
Per-1 是时钟基因之一,已知它可调节多种生物学事件,包括骨量的确定。甲状旁腺激素对骨骼具有合成代谢作用,但其作用机制尚未完全阐明。在这里,我们研究了在成骨细胞特异性甲状旁腺激素信号下 PTH 对 Per-1 基因表达的作用。在转基因小鼠中,特异性表达于成骨细胞的组成性激活甲状旁腺激素受体(caPPR)激活骨中的 Per-1 基因表达。这是特异性的,因为其他时钟基因 Bmal-1 的表达不受 caPPR 过表达的影响。Per-1 也在成骨细胞系中表达。有趣的是,Per-1 的表达是 PTH 信号诱导的 CRE 依赖性转录所必需的。这在 PTH 信号和骨中 Per-1 的合成代谢作用中形成了正反馈回路。这些数据表明,甲状旁腺激素在成骨细胞中的信号转导激活了体内 Per-1 基因的表达,与它在骨中的合成代谢作用至少部分通过转录事件的调节有关。