The effect of cortisol on bone cell differentiation.

The literature contains inconsistencies concerning the effect of corticosteroids on skeletal tissues. An in vitro system was developed to isolate the effects of cortisol on bone cell populations from those effects due to a secondary hyperparathyroidism. One hour prior to sacrifice, newborn mice were injected with tritiated-thymidine. The radii were placed into organ culture for four days. Effects of cortisol (0.0001, 0.01, 1.0 and 100.0 ug/ml media) and parathyroid extract (0.1, 1.0 and 10.0 units/ml media) on the bone cell populations were studied. Low doses of cortisol (0.0001 ug/ml media) stimulate progenitor cell mitosis and induce bone remodeling through increased differentiation of osteoblasts and osteoclasts. Higher doses of cortisol (above 1.0 ug/ml media) decreased progenitor cell mitosis, inhibit bone formation through decreased osteoblasts differentiation and preferentially protect and increase the resorbing cell population. Parathyroid extract, except at high levels (10 units PTE/ml media), stimulates progenitor cell mitosis and preferentially increases resorbing cell differentiation to the exclusion of osteoblast production. Cortisol and parathyroid extract can be seen to oppose each other in most effects on bone cell populations. While both increase resorbing cell populations, 45Ca metabolism of the whole bone in culture indicates that the activity of the individual cell is depressed by cortisol. Possible inter-relationships of the different bone cells through differentiation and modulation are discussed.