Up-regulation of inhibitors of DNA binding/differentiation gene during alendronate-induced osteoblast differentiation

Arch Gynecol Obstet. 2012 May;285(5):1331-8. doi: 10.1007/s00404-011-2141-1. Epub 2011 Nov 25.

Abstract

Purpose: To investigate the effect of alendronate on the expression of Id genes in osteoblast differentiation.

Methods: C2C12 cells were treated with alendronate for various concentrations and time periods. For evaluation of alendronate-induced osteoblast differentiation in C2C12 cells, alkaline phosphatase (ALP) activity was measured. The expression of osteoblast differentiation markers such as ALP, type-1 collagen (Col 1), and osteocalcin (OCN), and the expression of Id-1 and Id-2 were measured by RT-PCR. In order to understand the mechanism underlying the regulation of Id genes, the promoter region of the Id-1 gene was identified. Database analysis of the promoter region for Id-1 using known consensus sequences identified several putative response elements, including CCAAT/enhancer-binding protein beta (C/EBPβ).

Results: Alendronate treatment significantly increased not only ALP activity but also the expression of ALP, Col 1, and OCN, Id-1 and Id-2. C/EBPβ and alendronate cooperatively increased the promoter activity and expression of Id-1.

Conclusions: These results suggest that C/EBPβ-mediated Id-1 transcriptional activation may regulate alendronate-induced osteoblast differentiation of C2C12 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / pharmacology*
  • Alkaline Phosphatase / metabolism
  • Bone Density Conservation Agents / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Gene Expression
  • Humans
  • Inhibitor of Differentiation Proteins / genetics
  • Inhibitor of Differentiation Proteins / metabolism*
  • Osteoblasts / drug effects*
  • Up-Regulation

Substances

  • Bone Density Conservation Agents
  • Inhibitor of Differentiation Proteins
  • Alkaline Phosphatase
  • Alendronate