醋酸熊果酸对实验性牙周炎模型中小鼠骨形成的影响。

Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice.

机构信息

Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea.

Department of Oral and Maxillofacial Radiology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea.

出版信息

J Periodontal Res. 2019 Oct;54(5):533-545. doi: 10.1111/jre.12657. Epub 2019 Apr 15.

DOI:10.1111/jre.12657

PMID:30982986

Abstract

OBJECTIVE

We evaluated the role of oleanolic acid acetate (OAA), a triterpenoid commonly used in the treatment of liver disorders, inflammatory diseases, and metastasis, in bone formation after tooth loss by periodontitis.

BACKGROUND

Periodontitis causes the sequential degradation of the alveolar bone and associated structures, resulting in tooth loss. Several studies have attempted to regenerate the bone for implantation following tooth loss.

METHODS

Maxillary left second molar was extracted from 8-week-old male mice following induction of periodontitis by ligature for 5 days. The extraction socket was treated with 50 ng/µL OAA for 1, 2, and 3 weeks. Detailed morphological changes were examined using Masson's trichrome staining, and the precise localization patterns of various signaling molecules, including CD31, F4/80, interleukin (IL)-6, and osteocalcin, were observed. The volume of bone formation was examined by Micro-CT. Osteoclasts were enumerated using tartrate-resistant acid phosphatase (TRAP) staining. For molecular dissection of signaling molecules, we employed the hanging-drop in vitro cultivation method at E14 for 1 day and examined the expression pattern of transforming growth factor (TGF)-β superfamily and Wnt signaling genes.

RESULTS

Histomorphometrical examinations showed facilitated bone formation in the extraction socket following OAA treatment. In addition, OAA-treated specimens showed the altered localization patterns of inflammatory and bone formation-related signaling molecules including CD31, F4/80, IL-6, and osteocalcin. Also, embryonic tooth germ mesenchymal tissue cultivation with OAA treatment showed the significant altered expression patterns of signaling molecules such as transforming growth factor (TGF)-β superfamily and Wnt signaling.

CONCLUSIONS

Oleanolic acid acetate induces bone formation and remodeling through proper modulation of osteoblast, osteoclast, and inflammation with regulations of TGF-β and Wnt signaling.

摘要

目的

我们评估了齐墩果酸乙酸酯（OAA）在牙周炎导致牙齿缺失后的骨形成中的作用，OAA 是一种常用于治疗肝脏疾病、炎症性疾病和转移的三萜类化合物。

背景

牙周炎会导致牙槽骨及其相关结构的连续降解，导致牙齿脱落。已有多项研究试图在牙齿缺失后通过植入物再生骨。

方法

通过结扎诱导牙周炎，将 8 周龄雄性小鼠的上颌左第二磨牙在 5 天后拔除。用 50ng/µL OAA 处理拔牙窝 1、2 和 3 周。用 Masson 三色染色法检查详细的形态变化，并观察各种信号分子（包括 CD31、F4/80、白细胞介素 (IL)-6 和骨钙素）的精确定位模式。通过 Micro-CT 检查骨形成体积。用抗酒石酸酸性磷酸酶（TRAP）染色计数破骨细胞。为了对信号分子进行分子剖析，我们采用了 E14 日龄的悬滴体外培养法，培养 1 天，检查转化生长因子 (TGF)-β 超家族和 Wnt 信号基因的表达模式。

结果

组织形态学检查表明，OAA 处理后拔牙窝中的骨形成得到促进。此外，OAA 处理的标本显示出与炎症和骨形成相关的信号分子（包括 CD31、F4/80、IL-6 和骨钙素）的定位模式发生改变。此外，用 OAA 处理的胚胎牙胚间充质组织培养显示出信号分子（如 TGF-β 超家族和 Wnt 信号）的显著改变表达模式。