Pun K K
Department of Medicine, University of Hong Kong.
J Biochem. 1989 Dec;106(6):1090-3. doi: 10.1093/oxfordjournals.jbchem.a122970.
Loss of bone substance is a common manifestation of hyperparathyroidism. This suggests that parathyroid hormone (PTH) plays an important role as to bone mass. To investigate the mechanism underlying this change in bone mass, I studied the effects of PTH on collagen synthesis and mitogenesis of UMR-106 rat osteoblastic osteosarcoma cells. PTH inhibits the mitogenesis of UMR-106 rat osteosarcoma cells, the half-maximal concentration being 10(-8) to 10(-7) M, which is similar to the EC50 for cyclic AMP accumulation. Cyclic AMP, whose intracellular concentration was increased by PTH, plays a role in the modulation of mitogenesis, as shown by the comparable inhibitory effects of 8-bromoadenosine-3',5'-cyclic AMP (10(-4) M), forskolin (10(-7) M), and the phosphodiesterase inhibitor, IBMX (10(-5) M). PTH, in a similar concentration range, directly inhibited collagen synthesis. Concurrent with the suppression of collagen synthesis, the amounts of a1(I) and a2(I) collagen mRNA decreased proportionately. The results show that PTH modulates collagen synthesis at the transcriptional level. I concluded that parathyroid hormone inhibits the mitogenesis of osteoblasts as well as collagen synthesis by these cells. The decreases in the number of osteoblasts and the amount of collagen synthesis contribute to the loss of bone substance in hyperparathyroidism.
骨质流失是甲状旁腺功能亢进的常见表现。这表明甲状旁腺激素（PTH）在骨量方面起着重要作用。为了研究骨量这种变化的潜在机制，我研究了PTH对UMR - 106大鼠成骨细胞骨肉瘤细胞胶原蛋白合成和有丝分裂的影响。PTH抑制UMR - 106大鼠骨肉瘤细胞的有丝分裂，半数最大浓度为10（-8）至10（-7）M，这与环磷酸腺苷（cAMP）积累的EC50相似。PTH使细胞内cAMP浓度升高，cAMP在有丝分裂调节中起作用，如8 - 溴腺苷 - 3'，5'-环磷酸腺苷（10（-4）M）、福斯可林（10（-7）M）和磷酸二酯酶抑制剂异丁基甲基黄嘌呤（IBMX，10（-5）M）具有类似的抑制作用所示。在相似的浓度范围内，PTH直接抑制胶原蛋白合成。在抑制胶原蛋白合成的同时，α1（I）和α2（I）胶原蛋白mRNA的量成比例下降。结果表明，PTH在转录水平调节胶原蛋白合成。我得出结论，甲状旁腺激素抑制成骨细胞的有丝分裂以及这些细胞的胶原蛋白合成。成骨细胞数量的减少和胶原蛋白合成量的降低导致甲状旁腺功能亢进时的骨质流失。
