Qin Ling, Partridge Nicola C
Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
J Cell Biochem. 2005 Oct 15;96(3):632-40. doi: 10.1002/jcb.20550.
Parathyroid hormone (PTH), an anabolic agent for bone metabolism, has profound effects on gene expression in the osteoblast. Recently, we identified that amphiregulin (AR), an EGF-like ligand, is an immediate early gene for PTH treatment and has an important role in bone metabolism. In the present report, by using different PTH peptide fragments, protein kinase activators, and inhibitors, we have demonstrated that PTH regulates amphiregulin in a cAMP-protein kinase A (PKA)-dependent manner both in vitro and in vivo. We found that the phosphorylation of cAMP-response element (CRE)-binding protein (CREB) preceded AR transcription after PTH treatment. Moreover, luciferase reporter assays revealed that the binding of phosphorylated CREB to a conserved CRE site in the AR promoter plays an important role in basal, PTH-induced, and prostaglandin E2 (PGE2)-induced AR expression in osteoblastic cells. In summary, our data suggest that PTH-induced AR mRNA expression is mediated primarily through cAMP-PKA-CREB signaling.
甲状旁腺激素（PTH）是一种骨代谢的合成代谢剂，对成骨细胞中的基因表达有深远影响。最近，我们发现双调蛋白（AR），一种表皮生长因子样配体，是PTH治疗的即时早期基因，在骨代谢中起重要作用。在本报告中，通过使用不同的PTH肽片段、蛋白激酶激活剂和抑制剂，我们证明了PTH在体外和体内均以环磷酸腺苷-蛋白激酶A（PKA）依赖性方式调节双调蛋白。我们发现，PTH处理后，环磷酸腺苷反应元件（CRE）结合蛋白（CREB）的磷酸化先于AR转录。此外，荧光素酶报告基因检测显示，磷酸化的CREB与AR启动子中保守的CRE位点结合在成骨细胞中基础、PTH诱导和前列腺素E2（PGE2）诱导的AR表达中起重要作用。总之，我们的数据表明，PTH诱导的AR mRNA表达主要通过环磷酸腺苷-PKA-CREB信号传导介导。
