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Published on: August 17, 2015

Nuclear orphan receptor Nurr1 directly transactivates the osteocalcin gene in osteoblasts

Flavia Q Pirih1, Alan Tang, Ibrahim C Ozkurt

  • 1Division of Diagnostic and Surgical Sciences and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, CA 90095, USA.

The Journal of Biological Chemistry
|October 16, 2004
PubMed

Insights

Nurr1, a nuclear receptor, is induced by various signaling pathways in osteoblasts. This study shows Nurr1 directly regulates osteocalcin (Ocn) gene expression, identifying it as a key factor in bone cell gene regulation.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Bone Biology

Background:

  • Nurr1 is an NGFI-B nuclear orphan receptor that activates gene expression via NGFI-B response elements (NBREs).
  • Parathyroid hormone strongly induces Nurr1 in osteoblasts through the cAMP-protein kinase A pathway.
  • Understanding Nurr1's role in osteoblast gene regulation is crucial for bone biology.

Purpose of the Study:

  • To investigate the signaling pathways that induce Nurr1 expression in osteoblasts.
  • To determine if Nurr1 directly regulates the osteocalcin (Ocn) gene.
  • To elucidate Nurr1's role in the transcriptional regulation of osteoblastic genes.

Main Methods:

  • Osteoblasts were treated with various signaling pathway activators to assess Nurr1 induction.
  • Electrophoretic mobility shift assays (EMSAs) were used to study Nurr1 protein binding to NBREs and the Ocn promoter.
  • Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were employed to confirm Nurr1's regulatory role in Ocn expression.

Main Results:

  • cAMP-protein kinase A, protein kinase C, and calcium signaling pathways robustly induced Nurr1 in osteoblasts.
  • Nurr1 protein bound to a consensus NBRE and a specific NBRE-like site in the rat osteocalcin promoter.
  • Overexpression of Nurr1 induced Ocn expression, and this induction was dependent on the proximal NBRE-like site in the Ocn promoter.

Conclusions:

  • Osteocalcin (Ocn) is a direct target gene of Nurr1.
  • Nurr1 plays a significant role in the transcriptional regulation of osteoblastic gene expression.
  • Nurr1 acts as a core transcriptional factor in the regulation of bone cell function.

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