In vivo and in vitro effect of 1,25-dihydroxyvitamin D3 and 1,25-dihydroxy-16-ene-23-yne-vitamin D3 on the proliferation and differentiation of avian chondrocytes: their role in tibial dyschondroplasia.
In vivo and in vitro effect of 1,25-dihydroxyvitamin D3 and 1,25-dihydroxy-16-ene-23-yne-vitamin D3 on the proliferation and differentiation of avian chondrocytes: their role in tibial dyschondroplasia.
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1,25-二羟基维生素 D3 和 1,25-二羟基-16-烯-23-yne-维生素 D3 对禽软骨细胞增殖和分化的体内和体外作用：它们在胫骨软骨发育不良中的作用。
作者：
C. Farquharson;J. S. Rennie;N. Loveridge;C. Whitehead
1，25-二羟基维生素D3（1，25（OH）2D 3）被认为是胆钙化醇最具生物活性的代谢产物。它可以预防雏鸡胫骨软骨发育不良（TD），在这种情况下，生长板内的软骨细胞分化受到抑制。然而，目前尚不清楚其作用模式是通过与其软骨细胞受体的直接相互作用及其在细胞分化中的已知调节作用，还是通过增加钙吸收和动员来介导。已经合成了1，25（OH）2D 3的合成类似物，例如具有增加的分化特性但降低的钙血活性的1，25-二羟基-16-烯-23-炔胆钙化醇（RO 23-7553）。本研究观察了1，25（OH）_2D_3和RO 23-7553对鸡软骨细胞生长和分化的影响。此外，评估了这些类固醇在预防雏鸡TD中的体内有效性。1，25（OH）2D 3和RO 23-7553（10（-12）-10（-7）M）显示双相浓度效应，并且在体外调节软骨细胞增殖和分化方面具有相似的效力。然而，尽管1，25（OH）2D 3给药鸡的TD发生率（10%）低于对照鸡（55%），但RO 23-7553无效（50%）。这可能是由于与1，25（OH）2D 3相比，其对血浆维生素D结合蛋白（DBP）和软骨细胞受体的亲和力降低（低1000倍）。软骨细胞钙供应的减少也可能导致软骨细胞分化减少，但在RO 23-7553给药的禽类中，血液电离钙和血浆总钙均正常。这些数据表明RO 23-7553和1，25（OH）2D 3在体外但在体内不类似地调节软骨细胞增殖和分化。这可能是由体内两种类固醇的DBP结合和清除率差异引起的。
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) 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)2D3 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)2D3 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)2D3 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)2D3 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)2D3. 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)2D3 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.