Functional characterization of the parathyroid hormone 1 receptor in human periodontal ligament cells
Functional characterization of the parathyroid hormone 1 receptor in human periodontal ligament cells
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DOI：
10.1007/s00784-013-0985-4
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发表时间：
2014-03-01
影响因子：
3.4
通讯作者：
Jaeger, Andreas
中科院分区：
文献类型：
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作者：
Abuduwali, Nuersailike;Lossdoerfer, Stefan;Jaeger, Andreas
间歇性甲状旁腺激素（PTH）对骨产生合成代谢作用，已被批准用于骨质疏松症治疗。PTH的双重作用主要通过甲状旁腺激素1受体（PTH 1 R）介导。在配体结合后，PTH 1 R激活多种信号传导途径，包括cAMP/蛋白激酶A（PKA）-和磷脂酶C/蛋白激酶C（PLC/PKC）-依赖性途径。PTH 1 R在骨细胞中已被大量研究。本研究从细胞定位、结合亲和力、信号转导等方面对牙周膜细胞中PTH 1 R的表达进行了研究，并与成骨样细胞MG 63进行了比较，同时对牙周膜细胞和成骨样细胞MG 63中PTH 1 R的mRNA和蛋白进行了鉴定。PTH 1 R主要定位于质膜上，在细胞内的泡状结构，并在一定程度上，在两种细胞类型的细胞核。PTH 1 R的结合特征是细胞类型特异性的，PDL细胞表现出较低的结合亲和力。随着PTH（1-34）浓度的增加，MG 63细胞中cAMP和活性PKC的产生呈剂量依赖性，而PDL细胞中cAMP和活性PKC的产生呈双相调节。然而，我们观察到cAMP/PKA和PLC/PKC信号通路之间的串扰，它们在给定浓度的PTH（1-34）下被截然相反地调节。这些数据表明，尽管其亚细胞分布相似，但PDL细胞中的PTH 1 R表现出与MG 63细胞中的PTH 1 R不同的特征，指出这种受体的细胞类型特异性。这些发现进一步阐明了PTH在牙齿组织中的作用特点，并为合成代谢治疗策略的发展拓宽了理论基础。
Intermittent parathyroid hormone (PTH) exerts anabolic effects on bone and has been approved for osteoporosis therapy. The dual actions of PTH are mediated primarily through the parathyroid hormone 1 receptor (PTH1R). Upon ligand binding, PTH1R activates diverse signaling pathways, including cAMP/protein kinase A (PKA)- and phospholipase C/protein kinase C (PLC/PKC)-dependent pathways. PTH1R has been abundantly studied in bone cells. Knowledge on PTH1R characteristics and physiology in periodontal ligament (PDL) cells is still in its infancy.We characterized PTH1R in PDL cells in terms of its cellular localization, binding affinity, and signal transduction and compared these characteristics to those of MG63 osteoblast-like cells.PTH1R mRNA/protein was identified in PDL and MG63 cells. PTH1R was mainly localized on the plasma membrane, in vesicular structures inside the cell, and, to some extent, in the nucleus of both cell types. Binding characteristics of PTH1R were cell type specific, with PDL cells demonstrating a lower binding affinity. The response of cAMP and active PKC production in MG63 cells was dose dependent with increasing PTH(1-34) concentration, whereas in PDL cells, it was regulated biphasically. However, we observed a cross talk between the cAMP/PKA and PLC/PKC signaling pathways, which were regulated diametrically opposed at a given concentration of PTH(1-34).These data indicate that, albeit the similarity in its subcellular distribution, PTH1R in PDL cells exhibits characteristics different from those in MG63 cells, pointing to the cell type specificity of this receptor.The findings further elucidate the characteristics of PTH action in dental tissues and widen the theoretical basis for the development of anabolic treatment strategies.