Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the osteoblastic differentiation of the human osteosarcoma cell line SaOS-2.
The Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a hematopoietic growth factor that regulates the in vitro and in vivo proliferation and differentiation of hematopoietic cells through the interaction with a specific heterodimeric receptor complex (GM-CSFR), consisting of an alpha and a beta chain with molecular weights of 80 and 120 KDa, respectively. We have studied the expression of the GM-CSFR (alpha chain) on the surface of the human osteosarcoma cell line SaOS-2 and the in vitro effects of different concentrations (10, 100, and 200 ng/ml) of GM-CSF on GM-CSFR expression and the biological activity of SaOS-2 cells. Our data show that SaOS-2 cells express GM-CSFR and that GM-CSF can down-regulate the expression of its own receptor on these cells. Furthermore, to evaluate the biological effects of GM-CSF on SaOS-2 cells, we have investigated cell proliferation and differentiation of these cells treated with different doses of the growth factor through: (1) a morphological analysis of typical osteoblast differentiation markers such as osteopontin and BSP-II; (2) measurement of alkaline phosphatase (ALP) activity; (3) production of bone ECM components (collagen I, fibronectin, tenascin, and laminin); (4) production of interleukin-6 (IL-6) and osteocalcin in the culture medium. The results show that the in vitro treatment of SaOS-2 cells with recombinant human GM-CSF causes a decreased cell proliferation and an increased production of osteopontin, BSP-II, ALP, IL-6, and most but not all ECM components. These findings suggest that GM-CSF can regulate proliferation and differentiation of osteoblast-like SaOS-2 cells and could also play an unexpected role in the maturation of bone tissue.
Postiglione
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Dipartimento di Biologia e Patologia Cellulare, e Molecolare L. Califano, Italy. lorposti@unina.it
Domenico
G Di
GD
Montagnani
S
S
Spigna
G Di
GD
Salzano
S
S
Castaldo
C
C
Ramaglia
L
L
Sbordone
L
L
Rossi
G
G
D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins; D029607:Seminal Vesicle Secretory Proteins / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; C506895:SPP1 protein, human; D029607:Seminal Vesicle Secretory Proteins; D012795:Sialoglycoproteins; C424303:seminal vesicle secretory protein 109, Bos taurus; D053495:Osteopontin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor