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 biologically active metabolite of cholecalciferol. It prevents tibial dyschondroplasia (TD) in chicks where inhibition of chondrocyte differentiation 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 mediated by increased calcium absorption and mobilisation. Synthetic analogues of 1,25(OH)(2)D-3 such as 1,25-dihydroxy-16-ene-23-yne cholecalciferol (RO 23-7553) with increased differentiation properties but reduced 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 chondrocyte growth and differentiation were examined. In addition, the in 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 biphasic concentration effects and had similar potencies in vitro in regulating 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 plasma 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 differentiation but blood ionised and plasma total calcium were normal in birds dosed 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 binding and clearance rates of the two steroids in vivo.