Gli1 and axin2 are distinctive markers of human calvarial mesenchymal stromal cells in nonsyndromic craniosynostosis

Lorena Di Pietro, Marta Barba, Chiara Prampolini, Sabrina Ceccariglia, Paolo Frassanito, Alessia Vita, Enrico Guadagni, Davide Bonvissuto, Luca Massimi, Gianpiero Tamburrini, Ornella Parolini, Wanda Lattanzi

Research output: Contribution to journalArticlepeer-review


All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) provide progenitors for tissue growth and regeneration. They have been widely studied in long bones formed through endochondral ossification. Limited information is available on the composition of the osteogenic niche in flat bones (i.e., skull vault bones) that develop through direct membranous ossification. Craniosynostosis (CS) is a congenital craniofacial defect due to the excessive and premature ossification of skull vault sutures. This study aimed at analysing the expression of GLI1, AXIN2 and THY1 in the context of the human skull vault, using nonsyndromic forms of CS (NCS) as a model to test their functional implication in the aberrant osteogenic process. The expression of selected markers was studied in NCS patients’ calvarial bone specimens, to assess the in vivo location of cells, and in MSC isolated thereof. The marker expression profile was analysed during in vitro osteogenic differentiation to validate the functional implication. Our results show that GLI1 and AXIN2 are expressed in periosteal and endosteal locations within the osteogenic niche of human calvarial bones. Their expression is higher in MSC isolated from calvarial bones than in those isolated from long bones and tends to decrease upon osteogenic commitment and differentiation. In particular, AXIN2 expression was lower in cells isolated from prematurely fused sutures than in those derived from patent sutures of NCS patients. This suggests that AXIN2 could reasonably represent a marker for the stem cell population that undergoes depletion during the premature ossification process occurring in CS.

Original languageEnglish
Article number4356
Pages (from-to)1-19
Number of pages19
JournalInternational Journal of Molecular Sciences
Issue number12
Publication statusPublished - Jun 2 2020


  • AXIN2
  • Bone development
  • Cranial suture
  • GLI1
  • Mesenchymal stromal cells
  • Nonsyndromic craniosynostosis
  • Osteogenesis
  • Personalised medicine
  • Regenerative medicine
  • Stem cell niche

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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