Department of Orthodontics, Dental Clinic, University of Bonn, Germany.
J Periodontal Res. 2011 Jun;46(3):318-26. doi: 10.1111/j.1600-0765.2011.01345.x. Epub 2011 Feb 17.
Intermittent parathyroid hormone (PTH) is recognized as an anabolic agent in regenerative treatment strategies for bony tissues. Periodontal ligament (PDL) cells share features that are typical of osteoblasts, including an osteoblast-like response to stimulation with PTH, which implies a role for these cells in the regulation of repair processes following inflammatory periodontal disease. In the present study we explored the effect of intermittent administration of a PTH fragment [PTH(1-34)] on the osteoblastic differentiation of human PDL cells in vitro, and we investigated the signaling pathways used by the cells to mediate this effect.
PDL cells at two stages of confluence were characterized and used as a model for the role of cell maturation in the cellular response.
In preconfluent, less mature cultures, intermittent administration of PTH(1-34) and PTH(1-31) fragments increased alkaline phosphatase (ALP) activity and osteocalcin production, whereas intermittent administration of PTH(3-34) and PTH(7-34) had no effect. RO-32-0432, a specific protein kinase C inhibitor, did not inhibit the PTH(1-34) effect, whereas the protein kinase A inhibitor, H8, antagonized the PTH(1-34)-induced increase in ALP activity and osteocalcin. In contrast, in confluent, more mature cultures, intermittent administration of PTH(1-34), PTH(3-34) and PTH(7-34) fragments, but not of the PTH(1-31) fragment, decreased ALP activity, and osteocalcin and RO-32-0432, but not H8, inhibited the effect.
This study showed that the PTH(1-34) effect on ALP activity and osteocalcin production in human PDL cells is maturation state-dependent and specific in terms of the pathways involved. Whereas in less mature cells the PTH effect is associated with cyclic AMP/protein kinase A-dependent signaling, more mature cells seem to mediate the PTH signal primarily via protein kinase C-dependent pathways.
间歇性甲状旁腺激素（PTH）被认为是骨组织再生治疗策略中的一种合成代谢剂。牙周韧带（PDL）细胞具有成骨细胞的典型特征，包括对 PTH 刺激的成骨样反应，这意味着这些细胞在调节炎症性牙周病后的修复过程中发挥作用。在本研究中，我们探讨了间歇性给予 PTH 片段[PTH（1-34）]对体外人 PDL 细胞成骨分化的影响，并研究了细胞用于介导这种效应的信号通路。
我们对两个汇合阶段的 PDL 细胞进行了特征描述，并将其用作细胞成熟在细胞反应中作用的模型。
在未汇合、较不成熟的培养物中，间歇性给予 PTH（1-34）和 PTH（1-31）片段增加碱性磷酸酶（ALP）活性和骨钙素产生，而间歇性给予 PTH（3-34）和 PTH（7-34）则没有作用。RO-32-0432，一种特异性蛋白激酶 C 抑制剂，不能抑制 PTH（1-34）的作用，而蛋白激酶 A 抑制剂 H8 拮抗了 PTH（1-34）诱导的 ALP 活性和骨钙素增加。相比之下，在汇合、更成熟的培养物中，间歇性给予 PTH（1-34）、PTH（3-34）和 PTH（7-34）片段，但不给予 PTH（1-31）片段，降低了 ALP 活性，RO-32-0432 但不是 H8，抑制了该作用。
本研究表明，PTH（1-34）对人 PDL 细胞 ALP 活性和骨钙素产生的影响取决于细胞的成熟状态，涉及的途径具有特异性。在较不成熟的细胞中，PTH 效应与环磷酸腺苷/蛋白激酶 A 依赖性信号有关，而更成熟的细胞似乎主要通过蛋白激酶 C 依赖性途径介导 PTH 信号。
