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The effects of fibroblast growth factor-2 on human neonatal calvaria osteoblastic cells are differentiation stage specific.
J Bone Miner Res. 1998 Apr; 13(4):645-54.JB

Abstract

Fibroblast growth factors (FGFs) appear to play an important role in human cranial osteogenesis. We therefore investigated the effects of recombinant human FGF-2 (rhFGF-2) on human calvaria (HC) osteoblastic cells. Immunocytochemical analysis showed that confluent HC cells express both FGF receptors -1 and -2. In short-term culture, rhFGF-2 (0.1-100 ng/ml, 2-5 days) increased HC cell growth and decreased alkaline phosphatase (ALP) activity and type I collagen (ColI) synthesis, as evaluated by P1CP levels. When HC cells were induced to differentiate in long-term culture in the presence of 50 microg/ml ascorbic acid and 3 mM phosphate, HC cells initially proliferated, then ALP activity and ColI synthesis decreased and calcium content in the extracellular matrix increased. Continuous treatment with rhFGF-2 (50 ng/ml) for 1-28 days, or a transient rhFGF-2 treatment for 1-7 days, slightly increased DNA synthesis at 7 days, whereas a late treatment for 8-28 days had no effect on cell growth. The continuous and transient treatments with rhFGF-2 decreased ALP activity, ColI synthesis, and matrix mineralization. This was associated with a transient fall in osteocalcin (OC) production at 7 days. In contrast, the late rhFGF-2 treatment for 8-28 days only slightly inhibited ALP activity and increased matrix mineralization. In addition, both continuous and late treatments with rhFGF-2 increased OC production in more mature cells at 3-4 weeks of culture. We also found that the early and late treatments with rhFGF-2 had opposite effects on transforming growth factor beta2 production in proliferating cells and more mature cells. The results show that rhFGF-2 slightly stimulates cell growth and reduces the expression of osteoblast markers in less mature cells, whereas it induces OC production and matrix mineralization in more mature cells, indicating that the effects of FGF-2 are differentiation stage specific and that FGF-2 may modulate HC osteogenesis by acting at distinct stages of cell maturation.

Authors+Show Affiliations

INSERM Unit 349, Cell and Molecular Biology of Bone and Cartilage, and Department of Radioimmunology, Lariboisière Hospital, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9556064

Citation

Debiais, F, et al. "The Effects of Fibroblast Growth Factor-2 On Human Neonatal Calvaria Osteoblastic Cells Are Differentiation Stage Specific." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 13, no. 4, 1998, pp. 645-54.
Debiais F, Hott M, Graulet AM, et al. The effects of fibroblast growth factor-2 on human neonatal calvaria osteoblastic cells are differentiation stage specific. J Bone Miner Res. 1998;13(4):645-54.
Debiais, F., Hott, M., Graulet, A. M., & Marie, P. J. (1998). The effects of fibroblast growth factor-2 on human neonatal calvaria osteoblastic cells are differentiation stage specific. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 13(4), 645-54.
Debiais F, et al. The Effects of Fibroblast Growth Factor-2 On Human Neonatal Calvaria Osteoblastic Cells Are Differentiation Stage Specific. J Bone Miner Res. 1998;13(4):645-54. PubMed PMID: 9556064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of fibroblast growth factor-2 on human neonatal calvaria osteoblastic cells are differentiation stage specific. AU - Debiais,F, AU - Hott,M, AU - Graulet,A M, AU - Marie,P J, PY - 1998/4/29/pubmed PY - 1998/4/29/medline PY - 1998/4/29/entrez SP - 645 EP - 54 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 13 IS - 4 N2 - Fibroblast growth factors (FGFs) appear to play an important role in human cranial osteogenesis. We therefore investigated the effects of recombinant human FGF-2 (rhFGF-2) on human calvaria (HC) osteoblastic cells. Immunocytochemical analysis showed that confluent HC cells express both FGF receptors -1 and -2. In short-term culture, rhFGF-2 (0.1-100 ng/ml, 2-5 days) increased HC cell growth and decreased alkaline phosphatase (ALP) activity and type I collagen (ColI) synthesis, as evaluated by P1CP levels. When HC cells were induced to differentiate in long-term culture in the presence of 50 microg/ml ascorbic acid and 3 mM phosphate, HC cells initially proliferated, then ALP activity and ColI synthesis decreased and calcium content in the extracellular matrix increased. Continuous treatment with rhFGF-2 (50 ng/ml) for 1-28 days, or a transient rhFGF-2 treatment for 1-7 days, slightly increased DNA synthesis at 7 days, whereas a late treatment for 8-28 days had no effect on cell growth. The continuous and transient treatments with rhFGF-2 decreased ALP activity, ColI synthesis, and matrix mineralization. This was associated with a transient fall in osteocalcin (OC) production at 7 days. In contrast, the late rhFGF-2 treatment for 8-28 days only slightly inhibited ALP activity and increased matrix mineralization. In addition, both continuous and late treatments with rhFGF-2 increased OC production in more mature cells at 3-4 weeks of culture. We also found that the early and late treatments with rhFGF-2 had opposite effects on transforming growth factor beta2 production in proliferating cells and more mature cells. The results show that rhFGF-2 slightly stimulates cell growth and reduces the expression of osteoblast markers in less mature cells, whereas it induces OC production and matrix mineralization in more mature cells, indicating that the effects of FGF-2 are differentiation stage specific and that FGF-2 may modulate HC osteogenesis by acting at distinct stages of cell maturation. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/9556064/The_effects_of_fibroblast_growth_factor_2_on_human_neonatal_calvaria_osteoblastic_cells_are_differentiation_stage_specific_ L2 - https://doi.org/10.1359/jbmr.1998.13.4.645 DB - PRIME DP - Unbound Medicine ER -