Extracellular calcium chronically induced human osteoblasts effects: specific modulation of osteocalcin and collagen type XV.
Fluctuation in extracellular calcium (Ca(2+)) concentration occurs during bone remodeling. Free ionized Ca(2+) plays a critical role in regulating osteoblast functions. We analyzed the effects of different concentrations of free ionized Ca(2+) (0.5, 1.3, and 2.6 mM) 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 2.6 mM Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) on human osteoblasts and support the hypothesis of a direct role of this cation in the bone remodeling processes.
Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Bologna, Italy.
Elena
E
Gabusi
Cristina
C
Manferdini
Francesco
F
Grassi
Anna
A
Piacentini
Luca
L
Cattini
Giuseppe
G
Filardo
Elisabetta
E
Lambertini
Roberta
R
Piva
Nicoletta
N
Zini
Andrea
A
Facchini
Gina
G
Lisignoli
D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism*
C085811:COL15A1 protein, human; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D058574:Integrin-Binding Sialoprotein; C493709:RUNX2 protein, human; D015675:Osteocalcin; D003094:Collagen; D000469:Alkaline Phosphatase; D002118:Calcium