Volume 54, Issue 5 pp. 533-545
ORIGINAL ARTICLE

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

Nirpesh Adhikari

Nirpesh Adhikari

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

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Sanjiv Neupane

Sanjiv Neupane

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

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Yam Prasad Aryal

Yam Prasad Aryal

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

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Mi Choi

Mi Choi

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

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Wern-Joo Sohn

Wern-Joo Sohn

Pre-Major of Cosmetics and Pharmaceutics, Daegu Haany University, Gyeongsan, Korea

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Youngkyun Lee

Youngkyun Lee

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

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Jae-Kwang Jung

Jae-Kwang Jung

Department of Oral Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea

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Jung-Hong Ha

Jung-Hong Ha

Department of Conservative Dentistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea

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So-Young Choi

So-Young Choi

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

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Jo-Young Suh

Jo-Young Suh

Department of Periodontology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea

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Ji-Youn Kim

Ji-Youn Kim

Department of Dental Hygiene, College of Health Science, Gachon University, Incheon, Korea

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Mun-Chual Rho

Mun-Chual Rho

Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Korea

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Tae-Hoon Lee

Tae-Hoon Lee

Department of Oral Biochemistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Korea

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Hitoshi Yamamoto

Hitoshi Yamamoto

Department of Histology and Developmental Biology, Tokyo Dental College, Tokyo, Japan

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Chang-Hyeon An

Chang-Hyeon An

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

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Sang-Hyun Kim

Sang-Hyun Kim

Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Korea

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Seo-Young An

Corresponding Author

Seo-Young An

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

Correspondence

Jae-Young Kim, Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea.

Email: [email protected]

and

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

Email: [email protected]

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Jae-Young Kim

Corresponding Author

Jae-Young Kim

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

Correspondence

Jae-Young Kim, Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea.

Email: [email protected]

and

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

Email: [email protected]

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First published: 15 April 2019
Citations: 10
Seo-Young An and Jae-Young Kim have contributed equally to this work.

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.

CONFLICT OF INTEREST

The authors declare no conflicts of interests.

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