Differential effects of insulin-like growth factors I and II on growth, differentiation and glucoregulation in differentiating chondrocyte cells in culture.

Insulin-like growth factors I and II have been shown differentially to affect the growth and carbohydrate metabolism of differentiating cartilage developed from mouse embryonic limb buds in organ culture. To gain insight into the relative importance of IGF-I and II actions in different stages of development of cartilage we have established a primary culture of differentiating chondrocytes from mouse embryonic limb buds. Trypsin digested limb bud cells from 9-11 day old mouse embryos differentiated into chondrocytes by 5-7 days in culture. At all stages of differentiation, distinct receptors of IGF-I and II were observed. IGF-I stimulated growth and sulphate incorporation of the non-differentiated and differentiated chondrocytes. IGF-II stimulated growth of the non-differentiated cells and had no effect on growth or sulphate incorporation by the differentiated cells. IGF-II, however, stimulated the glucose uptake by the cells at all stages of differentiation. These data confirm our previous suggestion that IGF-I in cartilage is the regulator of growth and differentiation, while IGF-II may be an important regulator of glucose metabolism in the tissue.