Osteoblastic differentiation and cell calcification of adamantinomatous craniopharyngioma induced by bone morphogenetic protein-2

Cancer Biomark. 2017;18(2):191-198. doi: 10.3233/CBM-161576.

Abstract

Background: The calcification of adamantinomatous craniopharyngioma (ACP) often creates difficulties for surgical therapy. Nevertheless, the mechanism of ACP calcification is unclear. Our previous studies demonstrated that osteoblastic factors might play important roles in ACP calcification.

Objective: We examined the effects of recombinant human Bmp2 on ACP cell differentiation by testing osteoblastic proteins and calcium deposition.

Methods: The expression of osteoblastic factors including osteopontin (OPN), Runx2, and osterix in Bmp2-treated ACP cells was examined by western blot and/or real time PCR. ALP activity and calcium deposition after Bmp2 induction were also tested.

Results: Bmp2 significantly amplified the expression of Runx2, Osterix and OPN, as well as ALP activity. Both of these effects could be repressed by noggin treatment. Bmp2 also significantly induced the calcification of ACP, and noggin inhibited this calcium deposition.

Conclusion: Our study demonstrated for the first time that ACP cells could differentiate into an osteoblastic lineage via induction by Bmp2. The mechanism of ACP calcification likely involves osteoblastic differentiation modulated by Bmp2. Further studies targeting Bmp2 cascades could result in novel therapeutic interventions for recurrent ACP.

Keywords: Adamantinomatous craniopharyngioma calcification; bone morphogenetic protein-2; cell calcification; osteoblastic differentiation.

MeSH terms

  • Adolescent
  • Adult
  • Alkaline Phosphatase / metabolism
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Calcinosis / pathology
  • Cell Differentiation / drug effects
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Craniopharyngioma / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Osteoblasts / drug effects*
  • Osteoblasts / physiology
  • Osteopontin / genetics
  • Pituitary Neoplasms / pathology*
  • Recombinant Proteins / pharmacology
  • Sp7 Transcription Factor
  • Transcription Factors / genetics
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Core Binding Factor Alpha 1 Subunit
  • RUNX2 protein, human
  • Recombinant Proteins
  • SPP1 protein, human
  • Sp7 Transcription Factor
  • SP7 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Osteopontin
  • Alkaline Phosphatase