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

Nirpesh Adhikari; Sanjiv Neupane; Yam Prasad Aryal; Mi Choi; Wern Joo Sohn; Youngkyun Lee; Jae Kwang Jung; Jung Hong Ha; So Young Choi; Jo Young Suh; Ji Youn Kim; Mun Chual Rho; Tae Hoon Lee; Hitoshi Yamamoto; Chang Hyeon An; Sang Hyun Kim; Seo Young An; Jae Young Kim

doi:10.1111/jre.12657

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

Nirpesh Adhikari, Sanjiv Neupane, Yam Prasad Aryal, Mi Choi, Wern Joo Sohn, Youngkyun Lee, Jae Kwang Jung, Jung Hong Ha, So Young Choi, Jo Young Suh, Ji Youn Kim, Mun Chual Rho, Tae Hoon Lee, Hitoshi Yamamoto, Chang Hyeon An, Sang Hyun Kim, Seo Young An, Jae Young Kim

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11 Scopus citations

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.

Original language	English
Pages (from-to)	533-545
Number of pages	13
Journal	Journal of Periodontal Research
Volume	54
Issue number	5
DOIs	https://doi.org/10.1111/jre.12657
State	Published - 1 Oct 2019

Keywords

alveolar bone
chronic periodontitis
inflammation
regeneration

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10.1111/jre.12657

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Adhikari, N., Neupane, S., Aryal, Y. P., Choi, M., Sohn, W. J., Lee, Y., Jung, J. K., Ha, J. H., Choi, S. Y., Suh, J. Y., Kim, J. Y., Rho, M. C., Lee, T. H., Yamamoto, H., An, C. H., Kim, S. H., An, S. Y., & Kim, J. Y. (2019). Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice. Journal of Periodontal Research, 54(5), 533-545. https://doi.org/10.1111/jre.12657

@article{4c1d914b917a4d71af58e3d922d2cd21,

title = "Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice",

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.",

keywords = "alveolar bone, chronic periodontitis, inflammation, regeneration",

author = "Nirpesh Adhikari and Sanjiv Neupane and Aryal, {Yam Prasad} and Mi Choi and Sohn, {Wern Joo} and Youngkyun Lee and Jung, {Jae Kwang} and Ha, {Jung Hong} and Choi, {So Young} and Suh, {Jo Young} and Kim, {Ji Youn} and Rho, {Mun Chual} and Lee, {Tae Hoon} and Hitoshi Yamamoto and An, {Chang Hyeon} and Kim, {Sang Hyun} and An, {Seo Young} and Kim, {Jae Young}",

note = "Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",

year = "2019",

month = oct,

day = "1",

doi = "10.1111/jre.12657",

language = "English",

volume = "54",

pages = "533--545",

journal = "Journal of Periodontal Research",

issn = "0022-3484",

publisher = "Blackwell Munksgaard",

number = "5",

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Adhikari, N, Neupane, S, Aryal, YP, Choi, M, Sohn, WJ, Lee, Y , Jung, JK , Ha, JH , Choi, SY, Suh, JY, Kim, JY, Rho, MC, Lee, TH, Yamamoto, H, An, CH , Kim, SH , An, SY & Kim, JY 2019, 'Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice', Journal of Periodontal Research, vol. 54, no. 5, pp. 533-545. https://doi.org/10.1111/jre.12657

TY - JOUR

T1 - Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice

AU - Adhikari, Nirpesh

AU - Neupane, Sanjiv

AU - Aryal, Yam Prasad

AU - Choi, Mi

AU - Sohn, Wern Joo

AU - Lee, Youngkyun

AU - Jung, Jae Kwang

AU - Ha, Jung Hong

AU - Choi, So Young

AU - Suh, Jo Young

AU - Kim, Ji Youn

AU - Rho, Mun Chual

AU - Lee, Tae Hoon

AU - Yamamoto, Hitoshi

AU - An, Chang Hyeon

AU - Kim, Sang Hyun

AU - An, Seo Young

AU - Kim, Jae Young

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - alveolar bone

KW - chronic periodontitis

KW - inflammation

KW - regeneration

UR - http://www.scopus.com/inward/record.url?scp=85064505234&partnerID=8YFLogxK

U2 - 10.1111/jre.12657

DO - 10.1111/jre.12657

M3 - Article

C2 - 30982986

AN - SCOPUS:85064505234

SN - 0022-3484

VL - 54

SP - 533

EP - 545

JO - Journal of Periodontal Research

JF - Journal of Periodontal Research

IS - 5

ER -

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

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