Calcified Tissue International

, Volume 67, Issue 3, pp 247–254

Calcitonin Increases the Concentration of Insulin-Like Growth Factors in Serum-Free Cultures of Human Osteoblast-Line Cells

  • J.  Farley
  • H.P.  Dimai
  • B.  Stilt-Coffing
  • P.  Farley
  • T.  Pham
  • S.  Mohan
Article

DOI: 10.1007/s002230001112

Cite this article as:
Farley, J., Dimai, H., Stilt-Coffing, B. et al. Calcif Tissue Int (2000) 67: 247. doi:10.1007/s002230001112

Abstract

The current studies were intended to determine whether the anabolic effects of calcitonin (CT) on human osteoblast-line cells were (1) unique to osteosarcoma cells or also evident in osteoblast-line cells derived from normal human bone; and/or (2) associated with effects on several insulin-like growth factor (IGF) system components. Preliminary studies identified several osteoblastic cell lines, derived from normal human bone, which showed calcitonindependent increases in cell proliferation, alkaline phosphatase activity, and/or 45Ca uptake (P < 0.05–P < 0.001). Two of these cell lines—(human vertebrae) HBV-155 and HBV-163—were included with the human osteosarcoma cell line, SaOS-2, in most of our subsequent studies of calcitonin effects on selected IGF system components: IGF-II, IGF-I, and IGF binding proteins -3, -4, and -5. The results of those studies revealed that a 48 hour exposure to salmon CT caused a dose-dependent (0.03–3 mU/ml) increase in the net extracellular level of IGF-II (r = 0.96, P < 0.01) in serum-free cultures of SaOS-2 cells, with a maximal 60% increase at the highest tested dose (P < 0.02). Similar effects were seen with HBV-163 cells (r = 0.90, P < 0.01) and HBV-155 cells (r = 0.55, P < 0.02). The effect of calcitonin on the extracellular level of IGF-II was biphasic with respect to time: it decreased at 6 hours (P < 0.005 and P < 0.001, for SaOS-2 cells and HBV-163 cells, respectively) and increased at 24 hours (P < 0.02 and P < 0.05). These calcitonin-dependent increases in the extracellular level of IGF-II were associated with parallel increases in IGF-I (P < 0.005 for SaOS-2 cells and P < 0.03 for HBV-163 cells), but calcitonin did not affect the extracellular level of transforming growth factor (TGF)-β. The calcitonin-dependent changes in IGF-II were not associated with changes in the extracellular levels of IGF binding proteins -3, -4, or -5. Finally, our studies showed that two other members of the CT superfamily—CT gene-related peptide and amylin—did not mimic the effect of CT to increase the extracellular level of IGF-II. Together, these data demonstrate that human osteoblast-line cells derived from normal human bone can respond to CT, and that those responses can include CT dose- and time-dependent increases in the extracellular levels of IGF-I and IGF-II.

Copyright information

© Springer-Verlag New York 2000

Authors and Affiliations

  • J.  Farley
    • 1
  • H.P.  Dimai
    • 2
  • B.  Stilt-Coffing
    • 2
  • P.  Farley
    • 2
  • T.  Pham
    • 2
  • S.  Mohan
    • 1
  1. 1.Departments of Medicine and Biochemistry, Loma Linda University, Loma Linda, California, USAUS
  2. 2.Jerry L. Pettis Memorial Veterans Medical Center, 11201 Benton Street, Loma Linda, CaliforniaUS