Laboratory of Biopathology and Molecular Biology, University of Uberaba, Minas Gerais, Brazil.
Int Immunopharmacol. 2009 Sep;9(10):1150-8. doi: 10.1016/j.intimp.2009.06.002. Epub 2009 Jun 7.
Rosiglitazone (RGZ), an oral anti-hyperglycemic agent used for non-insulin-dependent diabetes mellitus, is a high-affinity synthetic agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Both in vitro and in vivo experiments have also revealed that RGZ possesses anti-inflammatory properties. Therefore, in the present study, we investigated the anti-inflammatory effects of RGZ in a rat model of periodontal disease induced by ligature placed around the mandible first molars of each animal. Male Wister rats were divided into four groups: 1) animals without ligature placement receiving administration of empty vehicle (control); 2) animals with ligature receiving administration of empty vehicle; 3) animals with ligature receiving administration with oral RGZ (10 mg/kg/day); and 4) animals with ligature receiving administration of subcutaneous RGZ (10 mg/kg/day). Thirty days after induction of periodontal disease, the animals were sacrificed, and mandibles and gingival tissues were removed for further analysis. An in vitro assay was also employed to test the inhibitory effects of RGZ on osteoclastogenesis. Histomorphological and immunohistochemical analyses of periodontal tissue demonstrated that RGZ-treated animals presented decreased bone resorption, along with reduced RANKL expression, compared to those animals with ligature, but treated with empty vehicle. Corresponding to such results obtained from in vivo experiments, RGZ also suppressed in vitro osteoclast differentiation in the presence of RANKL in MOCP-5 osteoclast precursor cells, along with the down-regulation of the expression of RANKL-induced TRAP mRNA. These data indicated that RGZ may suppress the bone resorption by inhibiting RANKL-mediated osteoclastogenesis elicited during the course of experimental periodontitis in rats.
罗格列酮（RGZ）是一种用于非胰岛素依赖型糖尿病的口服抗高血糖药物，是过氧化物酶体增殖物激活受体-γ（PPAR-γ）的高亲和力合成激动剂。体外和体内实验还表明，RGZ 具有抗炎作用。因此，在本研究中，我们在结扎下颌第一磨牙周围诱导的牙周病大鼠模型中研究了 RGZ 的抗炎作用。雄性 Wistar 大鼠分为四组：1）未结扎且给予空载体（对照组）的动物；2）结扎且给予空载体的动物；3）结扎且给予口服 RGZ（10mg/kg/天）的动物；4）结扎且给予皮下 RGZ（10mg/kg/天）的动物。牙周病诱导 30 天后，处死动物，取出下颌骨和牙龈组织进行进一步分析。还进行了体外实验来测试 RGZ 对破骨细胞形成的抑制作用。牙周组织的组织形态学和免疫组织化学分析表明，与用空载体治疗的结扎动物相比，RGZ 治疗的动物表现出减少的骨吸收，同时 RANKL 表达降低。与体内实验结果相对应，在 MOCP-5 破骨细胞前体细胞中存在 RANKL 的情况下，RGZ 还抑制体外破骨细胞分化，并下调 RANKL 诱导的 TRAP mRNA 的表达。这些数据表明，RGZ 可能通过抑制 RANKL 介导的破骨细胞发生来抑制大鼠实验性牙周炎过程中的骨吸收。
