Effects of Chromeceptin on Insulin-like Growth Factor II in Human Osteoblastic and Osteosarcoma Cells

Abstract

The insulin-like growth factor system is a complex regulatory system of insulin-like growth factors I and II (IGF-I and IGF-II) as well as their cell surface receptors and a family of insulin growth factor binding proteins (IGF-BPs). Despite extensive research on the IGF system in skeletal tissue, there is still not a complete understanding particularly of the role of IGF-II in the regulation of normal and pathological osseous cells in human skeletal biology. The purpose of this study was to further delineate the possible involvement of IGF-II in the regulation of human normal calvarial osteoblasts and G292 human osteosarcoma cellular activity using exogenously added IGF-II as well as a drug, Chromeceptin that has been shown in some other cellular systems to down regulate endogenous IGF-II levels.The results presented here show a similar dose dependent effect of Chromeceptin on inhibition of endogenous IGF-II levels (measured with an immunoassay) and cellular activity (measured with the MTT assay) in both the normal and osteosarcoma cells while small significant increases in activity with exogenously added IGF-II were observed only in the osteosarcoma cells. Moreover, IGF-BP1 levels (measured with an immunoassay) were shown to significantly increase in the G292 cells in a similar manner previously reported in other cell systems with only minor non-significant effects of exogenously added IGF-BP1 in the osteosarcoma cells studied here. These studies suggest that endogenous IGF-II is a critical regulator of activity in both normal and osteosarcoma cells and Chromeceptin can be an effective pharmacological agent for further studies on the role of the growth factor in human skeletal systems.