IN-VIVO AND IN-VITRO EFFECT OF 1,25-DIHYDROXYVITAMIN-D-3 AND 1,25-DIHYDROXY-16-ENE-23-YNE-VITAMIN-D-3 ON THE PROLIFERATION AND DIFFERENTIATION OF AVIAN CHONDROCYTES - THEIR ROLE IN TIBIAL DYSCHONDROPLASIA

1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3) is regarded as the most bio logically active metabolite of cholecalciferol. It prevents tibial dys chondroplasia (TD) in chicks where inhibition of chondrocyte different iation within the growth plate occurs. However, it is unclear whether its mode of action is through direct interaction with its chondrocyte receptor and its known regulatory role in cell differentiation or is m ediated by increased calcium absorption and mobilisation. Synthetic an alogues of 1,25(OH)(2)D-3 such as 1,25-dihydroxy-16-ene-23-yne choleca lciferol (RO 23-7553) with increased differentiation properties but re duced calcaemic activity have been synthesised. In this study, the in vitro and in vivo effects of 1,25(OH)(2)D-3 and RO 23-7553 on chick ch ondrocyte growth and differentiation were examined. In addition, the i n vivo effectiveness of these steroids in preventing TD in chicks was assessed. 1,25(OH)(2)D-3 and RO 23-7553 (10(-12)-10(-7) M) displayed b iphasic concentration effects and had similar potencies in vitro in re gulating chondrocyte proliferation and differentiation. However, while the incidence of TD in birds dosed with 1,25(OH)(2)D-3 was lower (10% ) than in control chicks (55%), RO 23-7553 was ineffective (50%). This may be the result of its reduced affinity (1000 times less) for the p lasma vitamin D binding protein (DBP) and the chondrocyte receptor in comparison to that of 1,25(OH)(2)D-3. A reduction in calcium supply to the chondrocyte may also result in decreased chondrocyte differentiat ion but blood ionised and plasma total calcium were normal in birds do sed with RO 23-7553. These data suggest that RO 23-7553 and 1,25(OH)(2 )D-3 regulate chondrocyte proliferation and differentiation similarly in vitro but not in vivo. This may be caused by differences in DBP bin ding and clearance rates of the two steroids in vivo.