Glibenclamide stimulates growth of human chondrocytes by IGF I dependent mechanisms.

Abstract

In rats and men the sulfonylurea glibenclamide augmented skeletal growth. However, with the design of the in vivo studies it was not possible to distinguish whether the growth promoting effect of glibenclamide was mediated by the augmented peripheral insulin or IGF-I levels or if the sulfonylurea had a direct effect on chondrocytes. We therefore measured clonal growth of isolated human chondrocytes in response to glibenclamide in vitro. Cells were isolated from human nose septal cartilage and incubated in a semi-solid medium. Colony formation in response to glibenclamide and IGF-I was determined. Glibenclamide stimulated clonal growth of chondrocytes in a bell-shaped fashion (p < 0.001). 50 ng/ml glibenclamide as the maximal dose augmented colony formation to 144 +/- 9% compared to clonal growth without glibenclamide in the incubation medium, which was designated as 100%. Basal values were obtained with 200 ng/ml glibenclamide. Insulin-like growth factor-I (IGF-I) at 3 ng/ml (118 +/- 4%) and 25 ng/ml (149 +/- 8%, p < 0.02) stimulated growth of chondrocytes. To elucidate the possible mechanism of glibenclamide on clonal growth, chondrocytes were incubated with the sulfonylurea and the IGF-I receptor antibody alpha IR-3. The antibody completely abolished the effect of glibenclamide on colony formation. The results suggest that the growth promoting effect of glibenclamide on isolated human chondrocytes is mediated by IGF-I dependent mechanisms.