The large functional spectrum of the heparin-binding cytokines MK and HB-GAM in continuously growing organs: The rodent incisor as a model

Thimios A. Mitsiadis, Javier Caton, Cosimo De Bari, Gilles Bluteau

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16 Citations (Scopus)


The heparin binding molecules MK and HB-GAM are involved in the regulation of growth and differentiation of many tissues and organs. Here we analyzed the expression of MK and HB-GAM in the developing mouse incisors, which are continuously growing organs with a stem cell compartment. Overlapping but distinct expression patterns for MK and HB-GAM were observed during all stages of incisor development (initiation, morphogenesis, cytodifferentiation). Both proteins were detected in the enamel knot, a transient epithelial signaling Structure that is important for tooth morphogenesis, and the cervical loop where the stem cell The functions of MK and HB-GAM were studied in dental explants and organotypic cultures niche is located. in vitro. in mesenchymal explants, MK stimulated HB-GAM expression and, vice-versa, HB-GAM upregulated MK expression, thus indicating a regulatory loop between these proteins. BMP and FGF molecules also activated expression of both cytokines in mesenchyme. The proliferative effects of MK and HB-GAM varied according to the mesenchymal OF epithelial Origin of the tissue. Growth, cytodifferentiation and mineralization were inhibited in incisor germs cultured in the presence of MK neutralizing antibodies. These results demonstrate that MK and HB-GAM are involved in stem cells maintenance, cytodifferentiation and mineralization processes during mouse incisor development. (C) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)256-266
Number of pages11
JournalDevelopmental Biology
Issue number1
Early online date22 May 2008
Publication statusPublished - 1 Aug 2008


  • midkine
  • HB-GAM
  • syndecan-1
  • FGF
  • odontoblast
  • dentin
  • tooth
  • incisor
  • stem cells
  • enamel knot
  • growth-associated molecule
  • epithelial-mesenchymal interactions
  • anaplastic lymphoma kinase
  • embryonic signaling center
  • activated protein-kinase
  • acid responsive gene
  • neural crest cells
  • retinoic acid
  • midkine MK
  • bone-formation

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