GLIBENCLAMIDE STIMULATES GROWTH OF HUMAN CHONDROCYTES BY IGF-I DEPENDENT MECHANISMS

In rats and men the sulfonylurea glibenclamide augmented skeletal grow th. However, with the design of the in vivo studies it was not possibl e 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 me asured clonal growth of isolated human chondrocytes in response to gli benclamide in vitro. Cells were isolated from human nose septal cartil age and incubated in a semi-solid medium. Colony formation in response to glibenclamide and IGF-I was determined. Glibenclamide stimulated c lonal 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 incu bation medium, which was designated as 100%. Basal values were obtaine d with 200 ng/ml glibenclamide. Insulin-like growth factor-I (IGF-I) a t 3 ng/ml(ll8 +/- 4%) and 25 ng/ml (149 +/- 8%, p < 0.02) stimulated g rowth of chondrocytes. To elucidate the possible mechanism of glibencl amide on clonal growth, chondrocytes were incubated with the sulfonylu rea and the IGF-I receptor antibody alpha IR-3. The antibody completel y abolished the effect of glibenclamide on colony formation. The resul ts suggest that the growth promoting effect of glibenclamide on isolat ed human chondrocytes is mediated by IGF-I dependent mechanisms.