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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Alendronate interacts with the inhibitory effect of 1,25(OH)2D3 on parathyroid hormone-related protein expression in human osteoblastic cells.
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Alendronate interacts with the inhibitory effect of 1,25(OH)2D3 on parathyroid hormone-related protein expression in human osteoblastic cells.

机译：阿仑膦酸盐与1,25（OH）2D3对人成骨细胞中甲状旁腺激素相关蛋白表达的抑制作用相互作用。

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摘要

The bisphosphonate alendronate is a potent inhibitor of bone resorption by its direct action on osteoclasts. In addition, there is some data suggesting that alendronate could also inhibit bone resorption indirectly by interacting with osteoblasts. Parathyroid hormone-related protein (PTHrP) produced by osteoblasts and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] are regulators of bone remodeling, which have interrelated actions in these cells. In this study, we assessed whether alendronate can affect PTHrP expression in the presence or absence of 1,25(OH)2D3 in human primary osteoblastic (hOB) cells from trabecular bone. Cell total RNA was isolated, and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was carried out using human PTHrP-specific primers. PTHrP in the hOB cell-conditioned medium was analyzed by a specific immunoradiometric assay. We found that PTHrP mRNA and secreted PTHrP were maximally inhibited by 10(-8) - 10(-6) M of 1,25(OH)2D3 treatment within 8-72 h in hOB cells.Alendronate (10(-14) - 10(-8) M) modified neither PTHrP mRNA nor PTHrP secretion, although it consistently abrogated the decrease in PTHrP production induced by 1,25(OH)2D3 in these cells. On the other hand, alendronate within the same dose range did not affect either the vitamin D receptor (VDR) mRNA or osteocalcin secretion, with or without 1,25(OH)2D3, in hOB cells. The inhibitory effect of alendronate on the 1,25(OH)2D3-induced decrease in PTHrP in these cells was mimicked by the calcium ionophore A23187 (5 x 10-6 M), while it was eliminated by 5 x 10(-5) M of nifedipine. Furthermore, although alendronate alone failed to affect [Ca2+]i in these cells, it stimulated [Ca2+]i after pretreatment of hOB cells with 10(-8) M of 1,25(OH)2D3, an effect that was abolished by 5 x 10(-5) M of nifedipine. These results show that alendronate disrupts the modulatory effect of 1,25(OH)2D3 on PTHrP production in hOB cells. Our findings indicate that an increase in calcium influx appears to be involved in the mechanism mediating this effect of alendronate.
机译：双膦酸盐阿仑膦酸盐通过直接作用于破骨细胞而成为有效的骨吸收抑制剂。此外，一些数据表明，阿仑膦酸盐还可以通过与成骨细胞相互作用间接抑制骨吸收。成骨细胞和1,25-二羟基维生素D3 [1,25（OH）2D3]产生的甲状旁腺激素相关蛋白（PTHrP）是骨重塑的调节剂，在这些细胞中具有相互关联的作用。在这项研究中，我们评估了在小梁骨人原代成骨细胞（hOB）中是否存在1,25（OH）2D3时，阿仑膦酸盐是否会影响PTHrP表达。分离细胞总RNA，并使用人PTHrP特异性引物进行半定量逆转录-聚合酶链反应（RT-PCR）。通过特异性免疫放射分析法分析了hOB细胞条件培养基中的PTHrP。我们发现hOB细胞在8-72小时内对1,25（OH）2D3的10（-8）-10（-6）M的处理最大程度地抑制了PTHrP mRNA和分泌的PTHrP.Alendronate（10（-14）- 10（-8）M）既不修饰PTHrP mRNA也不修饰PTHrP分泌，尽管它始终消除了1,25（OH）2D3在这些细胞中诱导的PTHrP产量的下降。另一方面，在hOB细胞中，相同剂量范围内的阿仑膦酸盐均不影响维生素D受体（VDR）mRNA或骨钙素分泌，无论是否存在1,25（OH）2D3。阿仑膦酸对这些细胞中1,25（OH）2D3诱导的PTHrP降低的抑制作用被钙离子载体A23187（5 x 10-6 M）模仿，而被5 x 10（-5）消除。硝苯地平的M。此外，尽管单独使用阿仑膦酸盐不能影响这些细胞中的[Ca2 +] i，但在用10（-8）M的1,25（OH）2D3预处理hOB细胞后，它刺激了[Ca2 +] i，这种作用被5废除了x 10（-5）M的硝苯地平。这些结果表明，阿仑膦酸盐破坏了1,25（OH）2D3对hOB细胞中PTHrP产生的调节作用。我们的发现表明钙内流的增加似乎与介导阿仑膦酸盐这种作用的机制有关。

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