Lossdörfer S, Stier S, Götz W, Jäger A
Department of Orthodontics, Dental Clinic, University of Bonn, Bonn, Germany.
J Periodontal Res. 2006 Feb;41(1):62-72. doi: 10.1111/j.1600-0765.2005.00838.x.
Parathyroid hormone (parathyroid hormone) has been shown to be capable of exerting anabolic effects on bone when administered intermittently. We hypothesized that parathyroid hormone will modulate the response of periodontal ligament cells in terms of anabolic effects with respect to proliferation, differentiation and the production of key regulatory factors of bone remodeling such as osteoprotegerin and receptor activator of nuclear factor kappaB ligand (RANKL) in a maturation-state dependent manner.
Periodontal ligament cells were cultured from human bicuspids obtained from six patients. Following characterization, confluent and preconfluent periodontal ligament cells were challenged with parathyroid hormone (1-34) for 0, 1, 3, 6 or 24 h within three incubation cycles of 48 h each. At harvest, the cell number, alkaline phosphatase specific activity and osteocalcin, osteoprotegerin and RANKL production were determined by means of semiquantitative polymerase chain reaction (PCR) and immunoassays. Dermal fibroblasts and MG63 osteoblast-like cells served as a reference.
Intermittent parathyroid hormone treatment of confluent periodontal ligament cells caused a significant increase in proliferation (+32% maximum) whereas alkaline phosphatase activity, osteocalcin and osteoprotegerin decreased at the transcriptional and translational level (-59.7% maximum). In preconfluent periodontal ligament cells, parathyroid hormone induced a decrease in proliferation (-66.3% maximum) but an increase in differentiation and osteoprotegerin production (+49.2% maximum). RANKL was hardly detectable and unaffected by parathyroid hormone treatment. Similar results were obtained in MG63 cells, whereas parathyroid hormone stimulation did not alter any of the parameters examined in dermal fibroblasts.
These results indicate that human periodontal ligament cells respond to an intermittent parathyroid hormone exposure with changes in proliferation, differentiation and osteoprotegerin production in a maturation-state dependent manner and therefore might be regulatorily involved in periodontal regeneration.
甲状旁腺激素已被证明间歇性给药时能够对骨骼发挥合成代谢作用。我们推测,甲状旁腺激素将以成熟状态依赖的方式,在增殖、分化以及骨重塑关键调节因子如骨保护素和核因子κB受体活化因子配体(RANKL)的产生方面,调节牙周膜细胞的合成代谢反应。
从6名患者拔除的双尖牙中培养牙周膜细胞。鉴定后,在每个48小时的三个培养周期内,用甲状旁腺激素(1-34)对融合和未融合的牙周膜细胞进行0、1、3、6或24小时的刺激。收获时,通过半定量聚合酶链反应(PCR)和免疫测定法测定细胞数量、碱性磷酸酶比活性以及骨钙素、骨保护素和RANKL的产生。皮肤成纤维细胞和MG63成骨样细胞作为对照。
间歇性甲状旁腺激素处理融合的牙周膜细胞导致增殖显著增加(最大增加32%),而碱性磷酸酶活性、骨钙素和骨保护素在转录和翻译水平下降(最大下降59.7%)。在未融合的牙周膜细胞中,甲状旁腺激素诱导增殖减少(最大减少66.3%),但分化和骨保护素产生增加(最大增加49.2%)。RANKL几乎检测不到,且不受甲状旁腺激素处理的影响。在MG63细胞中获得了类似结果,而甲状旁腺激素刺激未改变皮肤成纤维细胞中检测的任何参数。
这些结果表明,人牙周膜细胞对间歇性甲状旁腺激素暴露的反应是增殖、分化和骨保护素产生以成熟状态依赖的方式发生变化,因此可能在牙周再生中发挥调节作用。