Butyrate response factor 1 is regulated by parathyroid hormone and bone morphogenetic protein-2 in osteoblastic cells

Biochem Biophys Res Commun. 2004 Nov 5;324(1):218-23. doi: 10.1016/j.bbrc.2004.09.030.


Parathyroid hormone (PTH) exerts potent and diverse effects in bone and cartilage through activation of type 1 PTH receptors (PTH1R) capable of coupling to protein kinase A (PKA) and PKC. We have used macroarrays to identify zinc finger protein butyrate response factor-1 (BRF1) as a novel PTH regulated gene in clonal and normal osteoblasts of human and rodent origin. We further demonstrate that in human osteoblast-like OHS cells, biologically active hPTH(1-84) and hPTH(1-34) stimulate BRF1 mRNA expression in a dose- and time-dependent manner, while the amino-terminally truncated hPTH(3-84) which does not activate PTH1R has no effect. Moreover, using specific stimulators or inhibitors of PKA and PKC activity, the PTH-elicited BRF1 mRNA expression is mediated through the PKA signaling pathway. In mouse calvarial osteoblasts, BRF1 mRNA levels are upregulated by PTH(1-84) and reduced in response to bone morphogenetic protein 2 (BMP-2). Hence, our data showing that BRF1 is expressed in osteoblastic cells and regulated by PTH and BMP-2, suggest an important role for BRF1 in osteoblasts within the molecular network of PTH-dependent bone remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / metabolism
  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / metabolism*
  • Butyrate Response Factor 1
  • Cell Line, Tumor
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Hedgehog Proteins
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / physiology*
  • Osteosarcoma / metabolism
  • Parathyroid Hormone / metabolism*
  • Peptide Fragments / metabolism
  • Rats
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone / metabolism
  • Trans-Activators / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Zinc Fingers


  • BMP2 protein, human
  • Bmp2 protein, mouse
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Butyrate Response Factor 1
  • DNA-Binding Proteins
  • Hedgehog Proteins
  • Immediate-Early Proteins
  • PTH1R protein, human
  • Parathyroid Hormone
  • Peptide Fragments
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone
  • Trans-Activators
  • Transforming Growth Factor beta
  • ZFP36L1 protein, human
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Cyclic AMP-Dependent Protein Kinases