Regulation of alkaline phosphatase promoter activity by forkhead transcription factor FKHR

Int J Mol Med. 2002 Feb;9(2):147-52.

Abstract

Alkaline phosphatase (ALP) is a basic marker of osteoblast maturation and osteogenesis. However, the mechanisms of the ALP gene regulation in osteoblasts remain elusive. In this study, we examined the expression of forkhead transcription factor FKHR, a regulator of hepatic glucose metabolic and proapoptotic genes, in osteogenic cells and the effect of FKHR on transcription of the ALP gene. RT-PCR and immunoblot analyses revealed the expression of FKHR in osteogenic MC3T3-E1, SaOS2, and UMR 106 cells. Reporter assays demonstrated that the overexpression of FKHR stimulated ALP promoter activity through the forkhead response element in its promoter. These results suggest that ALP is a target gene regulated by FKHR and that FKHR contributes to osteoblast maturation and osteogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Alkaline Phosphatase / genetics*
  • Alkaline Phosphatase / metabolism
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Gene Expression Regulation*
  • Genes, Reporter
  • Mice
  • Osteoblasts / metabolism
  • Promoter Regions, Genetic / genetics*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Response Elements / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • DNA-Binding Proteins
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Foxo1 protein, mouse
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Transcription Factors
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Alkaline Phosphatase