title: New insights into the mechanism of abnormal calcification in nephrogenic systemic fibrosis - gadolinium promotes calcium deposition of mesenchymal stem cells and dermal fibroblasts.
abstract: BACKGROUND
  Recent studies have suggested that there is a close association between the administration of gadolinium (Gd)-based contrast agents and the development of nephrogenic systemic fibrosis (NSF), an acquired disorder characterized by systemic fibrosis and abnormal calcification in patients with severe renal dysfunction. However, the causative roles of Gd remain unknown.
  
  
  OBJECTIVE
  The aim of this in vitro study was to investigate the effect of Gd on the development of fibrosis and calcification in cultured cells.
  
  
  METHODS
  MC3T3-E1 cells (pre-osteoblastic cells), human adipose tissue-derived mesenchymal stem cells (HAMSCs), human subcutaneous preadipocytes, and human dermal fibroblasts (HDFs) were each cultured in differentiation medium with or without gadolinium chloride. Calcium deposition of MC3T3-E1 cells, HAMSCs, and HDFs was determined by alzarin red S staining. Adipogenic differentiation of human subcutaneous preadipocytes and HAMSCs was determined by oil red O staining. Fibrogenesis of HDFs was determined by real-time PCR to measure the mRNA expression of type I collagen. Cell proliferation was determined by MTS assay.
  
  
  RESULTS
  Gd induced calcium deposition in MC3T3-E1 cells, HAMSCs and HDFs in osteogenic differentiation media. Gd did not induce adipogenic differentiation in human subcutaneous preadipocytes and HAMSCs. Gd did not increase the mRNA expression of type I collagen in HDFs, but did promote cell proliferation.
  
  
  CONCLUSIONS
  We have demonstrated a direct effect of Gd on calcium deposition in cultured cells. The result will help us to understand the mechanism of abnormal calcification in NSF.
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Okada
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamanaka
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
mesh_terms: D016475:3T3 Cells; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002114:Calcinosis / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis / Q000473:pathology*; D005682:Gadolinium / Q000494:pharmacology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D054989:Nephrogenic Fibrosing Dermopathy / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology*
chemical_list: D003470:Culture Media; D005682:Gadolinium; D002118:Calcium