Extracellular calcium chronically induced human osteoblasts effects: Specific modulation of osteocalcin and collagen type XV

Elena Gabusi, Cristina Manferdini, Francesco Grassi, Anna Piacentini, Luca Cattini, Giuseppe Filardo, Elisabetta Lambertini, Roberta Piva, Nicoletta Zini, Andrea Facchini, Gina Lisignoli

Research output: Contribution to journalArticle


Fluctuation in extracellular calcium (Ca2+) concentration occurs during bone remodeling. Free ionized Ca2+ plays a critical role in regulating osteoblast functions. We analyzed the effects of different concentrations of free ionized Ca2+ (0.5, 1.3, and 2.6mM) on human osteoblasts and we evaluated osteoblastic phenotype (marker expression and cell morphology) and functions (osteogenic differentiation, cell proliferation, and cell signaling). Our data show human osteoblasts that chronically stimulated with 0.5, 1.3, or 2.6mM Ca2+ significantly increase intracellular content of alkaline phosphatase, collagen type I, osteocalcin, and bone sialoprotein, whereas collagen type XV was down-modulated and RUNX2 expression was not affected. We also found a Ca2+ concentration-dependent increase in osteogenic differentiation and cell proliferation, associated to an increase of signaling protein PLCβ1 and p-ERK. Human osteoblast morphology was affected by Ca2+ as seen by the presence of numerous nucleoli, cells in mitosis, cell junctions, and an increased number of vacuoles. In conclusion, our data show a clear phenotypical and functional effect of extracellular Ca2+ on human osteoblasts and support the hypothesis of a direct role of this cation in the bone remodeling processes.

Original languageEnglish
Pages (from-to)3151-3161
Number of pages11
JournalJournal of Cellular Physiology
Issue number8
Publication statusPublished - Aug 2012


ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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