Kirschneck Christian, Meier Matthias, Bauer Kathrin, Proff Peter, Fanghänel Jochen
Department of Orthodontics, University Medical Centre of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Anatomical Institute, Ernst-Moritz-Arndt University, Greifswald, Germany.
Cell Tissue Res. 2017 Apr;368(1):61-78. doi: 10.1007/s00441-016-2553-0. Epub 2017 Jan 3.
Non-steroidal anti-inflammatory drugs (NSAID) are used to alleviate pain sensations during orthodontic therapy but are also assumed to interfere with associated pseudo-inflammatory reactions. In particular, the effects of partially selective COX-2 inhibition over the constitutively expressed COX-1 (11:1) on periodontal cells and tissue, as induced by the NSAID meloxicam, remain unclear. We investigate possible adverse side-effects and potentially useful beneficial effects during orthodontic therapy and examine underlying cellular and tissue reactions. We randomly assigned 63 male Fischer344 rats to three consecutive experiments of 21 animals each (cone-beam computed tomography; histology/serology; reverse-transcription quantitative real-time polymerase chain reaction) in three experimental groups (n = 7; control; orthodontic tooth movement [OTM] of the first/second upper left molars [NiTi coil spring, 0.25 N]; OTM with a daily oral meloxicam dose of 3 mg/kg). In vitro, we stimulated human periodontal ligament fibroblasts (hPDL) with orthodontic pressure (2 g/cm) with/without meloxicam (10 μM). In vivo, meloxicam significantly reduced serum C-reactive protein concentration, tooth movement velocity, orthodontically induced dentine root resorption (OIRR), osteoclast activity and the relative expression of inflammatory/osteoclast marker genes within the dental-periodontal tissue, while presenting good gastric tolerance. In vitro, we observed a corresponding significant decrease of prostaglandin E/interleukin-6/RANKL(-OPG) expression and of hPDL-mediated osteoclastogenesis. By inhibiting prostaglandin synthesis, meloxicam seems to downregulate hPDL-mediated inflammation, RANKL-induced osteoclastogenesis and, consequently, tooth movement velocity by about 50%, thus limiting its suitability for analgesia during orthodontic therapy. However, its protective effects regarding OIRR and good tolerance profile suggest future prophylactic application, which merits its further investigation.
非甾体抗炎药（NSAID）用于缓解正畸治疗期间的疼痛感，但也被认为会干扰相关的假性炎症反应。特别是，NSAID美洛昔康诱导的部分选择性COX-2抑制对组成性表达的COX-1（11:1）对牙周细胞和组织的影响仍不清楚。我们研究正畸治疗期间可能的不良副作用和潜在有益作用，并检查潜在的细胞和组织反应。我们将63只雄性Fischer344大鼠随机分为三个连续实验，每个实验21只动物（锥形束计算机断层扫描；组织学/血清学；逆转录定量实时聚合酶链反应），分为三个实验组（n = 7；对照组；左上第一/第二磨牙正畸牙齿移动[镍钛螺旋弹簧，0.25 N]；每日口服美洛昔康剂量为3 mg/kg的正畸牙齿移动）。在体外，我们用正畸压力（2 g/cm）刺激人牙周膜成纤维细胞（hPDL），同时或不同时添加美洛昔康（10 μM）。在体内，美洛昔康显著降低血清C反应蛋白浓度、牙齿移动速度、正畸诱导的牙本质根吸收（OIRR）、破骨细胞活性以及牙周组织内炎症/破骨细胞标记基因的相对表达，同时具有良好的胃耐受性。在体外，我们观察到前列腺素E/白细胞介素-6/RANKL（-OPG）表达以及hPDL介导的破骨细胞生成相应显著降低。通过抑制前列腺素合成，美洛昔康似乎下调hPDL介导的炎症、RANKL诱导的破骨细胞生成，从而使牙齿移动速度降低约50%，因此限制了其在正畸治疗期间用于镇痛的适用性。然而，其对OIRR的保护作用和良好的耐受性表明其未来预防性应用值得进一步研究。
