Stimulating parathyroid cell proliferation and PTH release with phosphate in organ cultures obtained from patients with primary and secondary hyperparathyroidism for a prolonged period
Stimulating parathyroid cell proliferation and PTH release with phosphate in organ cultures obtained from patients with primary and secondary hyperparathyroidism for a prolonged period
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DOI：
10.1007/s00774-008-0032-8
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发表时间：
2009-03-01
影响因子：
3.3
通讯作者：
Sato, Kanji
中科院分区：
文献类型：
--
作者：
Nakajima, Kishiko;Umino, Ken-ichi;Sato, Kanji
原发性甲状旁腺功能亢进症（IA度-HPT）和继发性甲状旁腺功能亢进症（IIA度-HPT）的发病机制仍有待阐明。为了表征其病理生理学特征，我们研究了甲状旁腺组织器官培养物中钙和磷酸盐对细胞增殖和 PTH 释放的影响。从 IA 度-HPT（腺瘤）或 IIA 度-HPT（结节性增生）患者获得的解剖甲状旁腺组织在胶原涂层膜上预培养 1-4 周。将培养基更换为含有不同浓度磷酸盐的培养基后，研究了 PTH 释放和 [H-3] 胸苷掺入。与单层培养的分散甲状旁腺细胞相比，钙以浓度依赖性方式减少甲状旁腺组织中 PTH 的释放。此外，当IIA度-HPT获得的甲状旁腺组织预培养1-4周时，在高磷酸盐培养基中PTH释放和甲状旁腺细胞增殖显着增加。在从 IA 度-HPT 获得的甲状旁腺组织中也观察到了较小程度的磷酸盐效应，但 IA 度-HPT 和 IIA 度-HPT 之间没有显着差异。微阵列分析显示，IIA 度-HPT 中 PTH、CaSR 和 VDR 的 mRNA 水平保持良好，并且多种生长因子（例如 TGF-β1 诱导蛋白）大量表达。使用甲状旁腺功能亢进组织的器官培养物，其中 PTH 释放和 CaSR 长期保存良好，我们证明磷酸盐不仅在 IIA 度-HPT 中刺激甲状旁腺细胞增殖，而且在 IA 度-HPT 中也刺激甲状旁腺细胞增殖。尽管磷酸盐诱导细胞增殖的机制仍有待阐明，但我们的体外研究结果表明，两种甲状旁腺组织在某种程度上都保留了在正常甲状旁腺细胞中观察到的对高磷酸盐血症的生理反应系统。
The pathogenesis of primary hyperparathyroidism (IA degrees-HPT) and secondary hyperparathyroidism (IIA degrees-HPT) remains to be elucidated. To characterize their pathophysiology, we investigated the effects of calcium and phosphate on cell proliferation and PTH release in an organ culture of parathyroid tissues. Dissected parathyroid tissues obtained from patients with IA degrees-HPT (adenoma) or IIA degrees-HPT (nodular hyperplasia) were precultured on a collagen-coated membrane for 1-4 week. After changing the medium for one containing various concentrations of phosphate, PTH release and [H-3]thymidine incorporation were studied. In contrast to dispersed parathyroid cells cultured in a monolayer, calcium decreased PTH release in a concentration-dependent manner in parathyroid tissues. Furthermore, when parathyroid tissues obtained from IIA degrees-HPT were precultured for 1-4 weeks, PTH release and parathyroid cell proliferation were significantly increased in high-phosphate medium. These phosphate effects were also observed to a lesser extent in parathyroid tissues obtained from IA degrees-HPT, but there was no significant difference between IA degrees-HPT and IIA degrees-HPT. Microarray analyses revealed that mRNA levels of PTH, CaSR, and VDR were well preserved, and several growth factors (e.g. TGF-beta1-induced protein) were abundantly expressed in IIA degrees-HPT. Using organ cultures of hyperparathyroid tissues, in which PTH release and CaSR are well preserved for a prolonged period, we have demonstrated that phosphate stimulates parathyroid cell proliferation not only in IIA degrees-HPT but also in IA degrees-HPT. Although the mechanism responsible for phosphate-induced cell proliferation remains to be elucidated, our in vitro findings suggest that both parathyroid tissues preserve to some extent a physiological response system to hyperphosphatemia as observed in normal parathyroid cells.