The Prostacyclin Analog Iloprost Promotes Cementum Formation and Collagen Reattachment of Replanted Molars and Up-regulates Mineralization by Human Periodontal Ligament Cells

Sonntana Seang; Nichakorn Chenboonthai; Natnicha Nisaeh; Araya Teantongdee; Saharat Jamsai; Chanunchida Changgnam; Kanika Yoongkiew; Somchai Yodsanga; Paksinee Kamolratanakul; Sermporn Thaweesapphithak; Thantrira Pornthaveetus; Vincent Everts; Thanaphum Osathanont; Chalida Nakalekha Limjeerajarus

doi:10.1016/j.joen.2022.05.002

The Prostacyclin Analog Iloprost Promotes Cementum Formation and Collagen Reattachment of Replanted Molars and Up-regulates Mineralization by Human Periodontal Ligament Cells

Sonntana Seang, Nichakorn Chenboonthai, Natnicha Nisaeh, Araya Teantongdee, Saharat Jamsai, Chanunchida Changgnam, Kanika Yoongkiew, Somchai Yodsanga, Paksinee Kamolratanakul, Sermporn Thaweesapphithak, Thantrira Pornthaveetus, Vincent Everts, Thanaphum Osathanont, Chalida Nakalekha Limjeerajarus^*

^*Corresponding author for this work

Oral Cell Biology

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Introduction: This study evaluated the use of the prostacyclin analog iloprost as a root surface treatment agent in promoting acellular cementum (AC) formation and collagen reattachment after tooth replantation in vivo. In addition, its effect on human periodontal ligament cell (hPDLC) mineralization was assessed in vitro. Methods: First molars of 8-week-old Wistar rats were extracted. In 1 group, the root surfaces were treated with Hank's balanced salt solution (HBSS), and the other group's root surfaces were treated with 10⁻⁶ mol/L iloprost before replantation. At day 30, maxillae were prepared for micro–computed tomographic imaging and histomorphometric analysis. The effect of iloprost on mineralization by hPDLCs was analyzed by mineralized nodule formation and quantitative polymerase chain reaction at 7 and 14 days. Results: Micro–computed tomographic imaging demonstrated a significant higher bone volume in the iloprost groups, whereas the HBSS groups had extensive bone and root resorption. Histologic analysis revealed deposition of a thick AC layer along the root in the iloprost group with well-organized periodontal ligament fibers inserted into the cementum. The HBSS group demonstrated more osteoclasts than the iloprost group. In vitro, iloprost-treated hPDLCs had a significantly increased RUNX2, OSX, BSP, and ALP gene expression that coincided with an increased deposition of mineralized nodules. These effects were abrogated by a PGI₂ receptor inhibitor. Conclusions: Our results revealed that iloprost promoted PDL regeneration in replanted molars. Furthermore, resorption of the roots was decreased, whereas AC deposition was stimulated. Iloprost-treatment increased hPDLC mineralization and was mediated by PGI2 receptor activation. These observations indicate that iloprost may be a promising root surface treatment agent.

Original language	English
Pages (from-to)	1046-1054
Number of pages	9
Journal	Journal of endodontics
Volume	48
Issue number	8
Early online date	11 May 2022
DOIs	https://doi.org/10.1016/j.joen.2022.05.002
Publication status	Published - Aug 2022

Bibliographical note

Funding Information:
This project was supported by the National Research Council of Thailand (grant no. NRCT5-RSA63001-13 ); a dental faculty research grant (grant no. DRF62-001 ); and the Second Century Fund (C2F), Chulalongkorn University . We thank Biomaterial Testing Center; Assoc Prof Sutada Lotinun; Kevin Tompkins, DMD, PhD, Faculty of Dentistry, Chulalongkorn University; and H.E. Prof Ngy Meng for the kind assistance and advice. We also thank Prof Prasit Pavasant for his guidance in this study.

Funding Information:
This project was supported by the National Research Council of Thailand (grant no. NRCT5-RSA63001-13); a dental faculty research grant (grant no. DRF62-001); and the Second Century Fund (C2F), Chulalongkorn University. We thank Biomaterial Testing Center; Assoc Prof Sutada Lotinun; Kevin Tompkins, DMD, PhD, Faculty of Dentistry, Chulalongkorn University; and H.E. Prof Ngy Meng for the kind assistance and advice. We also thank Prof Prasit Pavasant for his guidance in this study. The authors deny any conflicts of interest related to this study.

Publisher Copyright:
© 2022 American Association of Endodontists

Funding

This project was supported by the National Research Council of Thailand (grant no. NRCT5-RSA63001-13 ); a dental faculty research grant (grant no. DRF62-001 ); and the Second Century Fund (C2F), Chulalongkorn University . We thank Biomaterial Testing Center; Assoc Prof Sutada Lotinun; Kevin Tompkins, DMD, PhD, Faculty of Dentistry, Chulalongkorn University; and H.E. Prof Ngy Meng for the kind assistance and advice. We also thank Prof Prasit Pavasant for his guidance in this study. This project was supported by the National Research Council of Thailand (grant no. NRCT5-RSA63001-13); a dental faculty research grant (grant no. DRF62-001); and the Second Century Fund (C2F), Chulalongkorn University. We thank Biomaterial Testing Center; Assoc Prof Sutada Lotinun; Kevin Tompkins, DMD, PhD, Faculty of Dentistry, Chulalongkorn University; and H.E. Prof Ngy Meng for the kind assistance and advice. We also thank Prof Prasit Pavasant for his guidance in this study. The authors deny any conflicts of interest related to this study.

Keywords

Acellular cementum regeneration
bone remodeling/regeneration
matrix mineralization
periodontal ligament
prostacyclin analog
tooth regeneration/transplantation

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10.1016/j.joen.2022.05.002

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Seang, S., Chenboonthai, N., Nisaeh, N., Teantongdee, A., Jamsai, S., Changgnam, C., Yoongkiew, K., Yodsanga, S., Kamolratanakul, P., Thaweesapphithak, S., Pornthaveetus, T., Everts, V., Osathanont, T., & Limjeerajarus, C. N. (2022). The Prostacyclin Analog Iloprost Promotes Cementum Formation and Collagen Reattachment of Replanted Molars and Up-regulates Mineralization by Human Periodontal Ligament Cells. Journal of endodontics, 48(8), 1046-1054. https://doi.org/10.1016/j.joen.2022.05.002

@article{fcdea419be3f47a38aa965e7ad8b0310,

title = "The Prostacyclin Analog Iloprost Promotes Cementum Formation and Collagen Reattachment of Replanted Molars and Up-regulates Mineralization by Human Periodontal Ligament Cells",

abstract = "Introduction: This study evaluated the use of the prostacyclin analog iloprost as a root surface treatment agent in promoting acellular cementum (AC) formation and collagen reattachment after tooth replantation in vivo. In addition, its effect on human periodontal ligament cell (hPDLC) mineralization was assessed in vitro. Methods: First molars of 8-week-old Wistar rats were extracted. In 1 group, the root surfaces were treated with Hank's balanced salt solution (HBSS), and the other group's root surfaces were treated with 10−6 mol/L iloprost before replantation. At day 30, maxillae were prepared for micro–computed tomographic imaging and histomorphometric analysis. The effect of iloprost on mineralization by hPDLCs was analyzed by mineralized nodule formation and quantitative polymerase chain reaction at 7 and 14 days. Results: Micro–computed tomographic imaging demonstrated a significant higher bone volume in the iloprost groups, whereas the HBSS groups had extensive bone and root resorption. Histologic analysis revealed deposition of a thick AC layer along the root in the iloprost group with well-organized periodontal ligament fibers inserted into the cementum. The HBSS group demonstrated more osteoclasts than the iloprost group. In vitro, iloprost-treated hPDLCs had a significantly increased RUNX2, OSX, BSP, and ALP gene expression that coincided with an increased deposition of mineralized nodules. These effects were abrogated by a PGI2 receptor inhibitor. Conclusions: Our results revealed that iloprost promoted PDL regeneration in replanted molars. Furthermore, resorption of the roots was decreased, whereas AC deposition was stimulated. Iloprost-treatment increased hPDLC mineralization and was mediated by PGI2 receptor activation. These observations indicate that iloprost may be a promising root surface treatment agent.",

keywords = "Acellular cementum regeneration, bone remodeling/regeneration, matrix mineralization, periodontal ligament, prostacyclin analog, tooth regeneration/transplantation",

author = "Sonntana Seang and Nichakorn Chenboonthai and Natnicha Nisaeh and Araya Teantongdee and Saharat Jamsai and Chanunchida Changgnam and Kanika Yoongkiew and Somchai Yodsanga and Paksinee Kamolratanakul and Sermporn Thaweesapphithak and Thantrira Pornthaveetus and Vincent Everts and Thanaphum Osathanont and Limjeerajarus, {Chalida Nakalekha}",

note = "Funding Information: This project was supported by the National Research Council of Thailand (grant no. NRCT5-RSA63001-13 ); a dental faculty research grant (grant no. DRF62-001 ); and the Second Century Fund (C2F), Chulalongkorn University . We thank Biomaterial Testing Center; Assoc Prof Sutada Lotinun; Kevin Tompkins, DMD, PhD, Faculty of Dentistry, Chulalongkorn University; and H.E. Prof Ngy Meng for the kind assistance and advice. We also thank Prof Prasit Pavasant for his guidance in this study. Funding Information: This project was supported by the National Research Council of Thailand (grant no. NRCT5-RSA63001-13); a dental faculty research grant (grant no. DRF62-001); and the Second Century Fund (C2F), Chulalongkorn University. We thank Biomaterial Testing Center; Assoc Prof Sutada Lotinun; Kevin Tompkins, DMD, PhD, Faculty of Dentistry, Chulalongkorn University; and H.E. Prof Ngy Meng for the kind assistance and advice. We also thank Prof Prasit Pavasant for his guidance in this study. The authors deny any conflicts of interest related to this study. Publisher Copyright: {\textcopyright} 2022 American Association of Endodontists",

year = "2022",

month = aug,

doi = "10.1016/j.joen.2022.05.002",

language = "English",

volume = "48",

pages = "1046--1054",

journal = "Journal of endodontics",

issn = "0099-2399",

publisher = "Elsevier Inc.",

number = "8",

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Seang, S, Chenboonthai, N, Nisaeh, N, Teantongdee, A, Jamsai, S, Changgnam, C, Yoongkiew, K, Yodsanga, S, Kamolratanakul, P, Thaweesapphithak, S, Pornthaveetus, T, Everts, V, Osathanont, T & Limjeerajarus, CN 2022, 'The Prostacyclin Analog Iloprost Promotes Cementum Formation and Collagen Reattachment of Replanted Molars and Up-regulates Mineralization by Human Periodontal Ligament Cells', Journal of endodontics, vol. 48, no. 8, pp. 1046-1054. https://doi.org/10.1016/j.joen.2022.05.002

The Prostacyclin Analog Iloprost Promotes Cementum Formation and Collagen Reattachment of Replanted Molars and Up-regulates Mineralization by Human Periodontal Ligament Cells. / Seang, Sonntana; Chenboonthai, Nichakorn; Nisaeh, Natnicha et al.
In: Journal of endodontics, Vol. 48, No. 8, 08.2022, p. 1046-1054.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - The Prostacyclin Analog Iloprost Promotes Cementum Formation and Collagen Reattachment of Replanted Molars and Up-regulates Mineralization by Human Periodontal Ligament Cells

AU - Seang, Sonntana

AU - Chenboonthai, Nichakorn

AU - Nisaeh, Natnicha

AU - Teantongdee, Araya

AU - Jamsai, Saharat

AU - Changgnam, Chanunchida

AU - Yoongkiew, Kanika

AU - Yodsanga, Somchai

AU - Kamolratanakul, Paksinee

AU - Thaweesapphithak, Sermporn

AU - Pornthaveetus, Thantrira

AU - Everts, Vincent

AU - Osathanont, Thanaphum

AU - Limjeerajarus, Chalida Nakalekha

N1 - Funding Information: This project was supported by the National Research Council of Thailand (grant no. NRCT5-RSA63001-13 ); a dental faculty research grant (grant no. DRF62-001 ); and the Second Century Fund (C2F), Chulalongkorn University . We thank Biomaterial Testing Center; Assoc Prof Sutada Lotinun; Kevin Tompkins, DMD, PhD, Faculty of Dentistry, Chulalongkorn University; and H.E. Prof Ngy Meng for the kind assistance and advice. We also thank Prof Prasit Pavasant for his guidance in this study. Funding Information: This project was supported by the National Research Council of Thailand (grant no. NRCT5-RSA63001-13); a dental faculty research grant (grant no. DRF62-001); and the Second Century Fund (C2F), Chulalongkorn University. We thank Biomaterial Testing Center; Assoc Prof Sutada Lotinun; Kevin Tompkins, DMD, PhD, Faculty of Dentistry, Chulalongkorn University; and H.E. Prof Ngy Meng for the kind assistance and advice. We also thank Prof Prasit Pavasant for his guidance in this study. The authors deny any conflicts of interest related to this study. Publisher Copyright: © 2022 American Association of Endodontists

PY - 2022/8

Y1 - 2022/8

N2 - Introduction: This study evaluated the use of the prostacyclin analog iloprost as a root surface treatment agent in promoting acellular cementum (AC) formation and collagen reattachment after tooth replantation in vivo. In addition, its effect on human periodontal ligament cell (hPDLC) mineralization was assessed in vitro. Methods: First molars of 8-week-old Wistar rats were extracted. In 1 group, the root surfaces were treated with Hank's balanced salt solution (HBSS), and the other group's root surfaces were treated with 10−6 mol/L iloprost before replantation. At day 30, maxillae were prepared for micro–computed tomographic imaging and histomorphometric analysis. The effect of iloprost on mineralization by hPDLCs was analyzed by mineralized nodule formation and quantitative polymerase chain reaction at 7 and 14 days. Results: Micro–computed tomographic imaging demonstrated a significant higher bone volume in the iloprost groups, whereas the HBSS groups had extensive bone and root resorption. Histologic analysis revealed deposition of a thick AC layer along the root in the iloprost group with well-organized periodontal ligament fibers inserted into the cementum. The HBSS group demonstrated more osteoclasts than the iloprost group. In vitro, iloprost-treated hPDLCs had a significantly increased RUNX2, OSX, BSP, and ALP gene expression that coincided with an increased deposition of mineralized nodules. These effects were abrogated by a PGI2 receptor inhibitor. Conclusions: Our results revealed that iloprost promoted PDL regeneration in replanted molars. Furthermore, resorption of the roots was decreased, whereas AC deposition was stimulated. Iloprost-treatment increased hPDLC mineralization and was mediated by PGI2 receptor activation. These observations indicate that iloprost may be a promising root surface treatment agent.

AB - Introduction: This study evaluated the use of the prostacyclin analog iloprost as a root surface treatment agent in promoting acellular cementum (AC) formation and collagen reattachment after tooth replantation in vivo. In addition, its effect on human periodontal ligament cell (hPDLC) mineralization was assessed in vitro. Methods: First molars of 8-week-old Wistar rats were extracted. In 1 group, the root surfaces were treated with Hank's balanced salt solution (HBSS), and the other group's root surfaces were treated with 10−6 mol/L iloprost before replantation. At day 30, maxillae were prepared for micro–computed tomographic imaging and histomorphometric analysis. The effect of iloprost on mineralization by hPDLCs was analyzed by mineralized nodule formation and quantitative polymerase chain reaction at 7 and 14 days. Results: Micro–computed tomographic imaging demonstrated a significant higher bone volume in the iloprost groups, whereas the HBSS groups had extensive bone and root resorption. Histologic analysis revealed deposition of a thick AC layer along the root in the iloprost group with well-organized periodontal ligament fibers inserted into the cementum. The HBSS group demonstrated more osteoclasts than the iloprost group. In vitro, iloprost-treated hPDLCs had a significantly increased RUNX2, OSX, BSP, and ALP gene expression that coincided with an increased deposition of mineralized nodules. These effects were abrogated by a PGI2 receptor inhibitor. Conclusions: Our results revealed that iloprost promoted PDL regeneration in replanted molars. Furthermore, resorption of the roots was decreased, whereas AC deposition was stimulated. Iloprost-treatment increased hPDLC mineralization and was mediated by PGI2 receptor activation. These observations indicate that iloprost may be a promising root surface treatment agent.

KW - Acellular cementum regeneration

KW - bone remodeling/regeneration

KW - matrix mineralization

KW - periodontal ligament

KW - prostacyclin analog

KW - tooth regeneration/transplantation

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The Prostacyclin Analog Iloprost Promotes Cementum Formation and Collagen Reattachment of Replanted Molars and Up-regulates Mineralization by Human Periodontal Ligament Cells

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