RANKL inhibition through osteoprotegerin blocks bone loss in experimental periodontitis
RANKL inhibition through osteoprotegerin blocks bone loss in experimental periodontitis
复制标题
DOI：
10.1902/jop.2007.070073
复制
发表时间：
2007-07-01
影响因子：
4.3
通讯作者：
Giannobile, William V.
中科院分区：
文献类型：
--
作者：
Jin, Qiming;Cirelli, Joni A.;Giannobile, William V.
背景：预防牙槽骨破坏是牙周病治疗中的一个临床难题。核因子-kappa B受体激活剂(RANKL)抑制剂骨保护素(OPG)抑制破骨细胞生成，抑制骨吸收。方法：采用实验性牙周炎结扎模型，研究RANKL抑制对牙槽骨丢失的影响。32只大鼠给予人OPG-Fc融合蛋白(10 mg/kg)或赋形剂皮下注射，每周2次，连续6周。阴性和阳性对照分别没有接受任何治疗或通过车辆递送疾病。分别于术后3周和6周取材，进行下颌骨的显微CT检查和组织学检查。采用酶联免疫吸附试验检测血清OPGFc和抗酒石酸酸性磷酸酶-5b(TRAP-5b)水平。统计分析包括方差分析(ANOVA)和Tukey检验。结果：OPGFc处理的动物在第3天和整个研究过程中都在血清中检测到人OPG-Fc。OPG-FC给药后，血清TRAP-5b水平显著降低，并在观察期内一直维持在较低水平。在第3周和第6周，OPG-FC组动物的牙槽骨体积与对照组相比有显著的保存(P
Background: Prevention of alveolar bone destruction is a clinical challenge in periodontal disease treatment. The receptor activator of nuclear factor-kappa B ligand (RANKL) inhibitor osteoprotegerin (OPG) inhibits osteoclastogenesis and suppresses bone resorption.Methods: To study the effects of RANKL inhibition on alveolarbone loss, an experimental ligature- induced model of periodontitis was used. A total of 32 rats were administered human OPG-Fc fusion protein (10 mg/kg) or vehicle by subcutaneous delivery twice weekly for 6 weeks. Negative or positive controls received no treatment or disease through vehicle delivery, respectively. Biopsies were harvested after 3 and 6 weeks, and mandibulae were evaluated by microcomputed tomography (mu CT) and histology. Serum levels of human OPGFc and tartrate- resistant acid phosphatase-5b (TRAP-5b) were measured throughout the study by enzyme-linked immunosorbent assay (ELISA). Statistical analyses included analysis of variance (ANOVA) and Tukey tests.Results: Human OPG-Fc was detected in the sera of OPGFc-treated animals by 3 days and throughout the study. Serum TRAP-5b was sharply decreased by OPG-Fc treatment soon after OPG -Fc delivery and remained low for the observation period. Significant preservation of alveolar bone volume was observed among OPG-Fc-treated animals compared to the controls at weeks 3 and 6 (P