CALCITONIN ACUTELY INCREASES NET CA-45 UPTAKE AND ALTERS ALKALINE-PHOSPHATASE SPECIFIC ACTIVITY IN HUMAN OSTEOSARCOMA CELLS

Altnough the primary skeletal action of exogenous calcitonin is to inhibit bone resorption, calcitonin also has effects on bone formation. In-vitro data indicate that the latter may include direct effects on bone cells of osteoblastic lineage. In the current studies, we examined the effects of calcitonin on cyclic adenosine monophosphate (cAMP) and PGE2 synthesis and 45Ca uptake in human osteosarcoma cells, specifically, TE-85 cells and subpopulations of SaOS-2 cells with low-, intermediate-, and high-steady-state levels of skeletal alkaline phosphatase (ALP) activity. Since previous in-vivo studies had shown that calcitonin could acutely decrease skeletal ALP activity in rat periosteal osteoblasts, we also measured the effects of calcitonin treatment on ALP specific activity. Neither salmon nor human calcitonin altered the net synthesis of cAMP or PGE2 by SaOS-2 cells, but human calcitonin gene-related peptide increased both (P < .001 and P < .005, respectively). Both salmon and human calcitonin had short-term effects to alter ALP activity in TE-85 and SaOS-2 cells. The effects were different in SaOS-2 subpopulations with different pretreatment ALP levels. Four hours of exposure to salmon calcitonin had dose-dependent, biphasic effects on ALP levels in SaOS-2 cells with intermediate pretreatment ALP levels, increasing ALP at doses between 0.16 and 1.6 nmol/L (P < .005) and decreasing ALP at higher concentrations (P < .05). Both salmon and human calcitonin, but not human calcitonin gene-related peptide, also had short-term effects to increase net 45Ca uptake by SaOS-2 cells; these effects were dose-dependent and long-lasting. Salmon calcitonin (8 pmol/L) increased net 45Ca uptake within 10 minutes (242% of control, P < .001), and the effect was still apparent after 4 hours of continuous exposure (151% of control, P < .01); similar effects were seen with TE-8t cells. The effect of calcitonin to increase net 45Ca uptake by SaOS-2 cells could be obeserved in (Fitton-Jackson-modified) Biggers-Gwatkin-Jones culture medium (BGJb) containing 1.5 or 2.0 mmol/L Ca, but not in medium containing 0.5 or 1.0 mmol/L Ca, or in the presence of 10 μmol/L verapamil. © 1993.