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Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase

Massive production of reactive oxygen species (ROS) in human periodontal ligament fibroblasts (HPdLFs) by nitrogen-containing bisphosphonates (BPs) is the main factor causing BP-related osteonecrosis of the jaw. Further, oxidative stress and apoptosis of fibroblasts induced by ROS are closely associ...

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Autores principales: Liu, Di, Du, Juan, Sun, Jing, Li, Minqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806876/
https://www.ncbi.nlm.nih.gov/pubmed/34024253
http://dx.doi.org/10.1080/21655979.2021.1928930
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author Liu, Di
Du, Juan
Sun, Jing
Li, Minqi
author_facet Liu, Di
Du, Juan
Sun, Jing
Li, Minqi
author_sort Liu, Di
collection PubMed
description Massive production of reactive oxygen species (ROS) in human periodontal ligament fibroblasts (HPdLFs) by nitrogen-containing bisphosphonates (BPs) is the main factor causing BP-related osteonecrosis of the jaw. Further, oxidative stress and apoptosis of fibroblasts induced by ROS are closely associated with the activation of MAPK. Parathyroid hormone-related protein (PTHrP) can block the activity of MAPK by regulating the levels of MAPK phosphatase 1 (MKP1). Therefore, it is speculated that PTHrP can inhibit the apoptosis of HPdLFs caused by nitrogen-containing BP via regulating the expression levels of MKP1. Herein, alendronate sodium salt trihydrate (nitrogen-containing BP, FOS) and HPdLFs were co-cultured for 24 h, 48 h, and 72 h, and the levels of ROS and apoptosis were determined, respectively. After 48 h co-culture, FOS significantly increased the levels of ROS and apoptosis, and high phosphorylation levels of p38, ERK1/2 and p66(Shc) were found in this study. However, the inhibitors of p38 and ERK1/2 significantly reduced the apoptosis of HPdLFs. Interestingly, PTHrP pre-treatment significantly reduced the phosphorylation levels of p38, ERK1/2, and p66(Shc). More importantly, MKP1 inhibitor sanguinarine inhibited the dephosphorylation levels of p38, ERK1/2, and p66(Shc) caused by PTHrP. Altogether, PTHrP can inhibit nitrogen-containing BP-induced apoptosis of HPdLFs by activating MKP1 phosphatase.
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spelling pubmed-88068762022-02-02 Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase Liu, Di Du, Juan Sun, Jing Li, Minqi Bioengineered Research Paper Massive production of reactive oxygen species (ROS) in human periodontal ligament fibroblasts (HPdLFs) by nitrogen-containing bisphosphonates (BPs) is the main factor causing BP-related osteonecrosis of the jaw. Further, oxidative stress and apoptosis of fibroblasts induced by ROS are closely associated with the activation of MAPK. Parathyroid hormone-related protein (PTHrP) can block the activity of MAPK by regulating the levels of MAPK phosphatase 1 (MKP1). Therefore, it is speculated that PTHrP can inhibit the apoptosis of HPdLFs caused by nitrogen-containing BP via regulating the expression levels of MKP1. Herein, alendronate sodium salt trihydrate (nitrogen-containing BP, FOS) and HPdLFs were co-cultured for 24 h, 48 h, and 72 h, and the levels of ROS and apoptosis were determined, respectively. After 48 h co-culture, FOS significantly increased the levels of ROS and apoptosis, and high phosphorylation levels of p38, ERK1/2 and p66(Shc) were found in this study. However, the inhibitors of p38 and ERK1/2 significantly reduced the apoptosis of HPdLFs. Interestingly, PTHrP pre-treatment significantly reduced the phosphorylation levels of p38, ERK1/2, and p66(Shc). More importantly, MKP1 inhibitor sanguinarine inhibited the dephosphorylation levels of p38, ERK1/2, and p66(Shc) caused by PTHrP. Altogether, PTHrP can inhibit nitrogen-containing BP-induced apoptosis of HPdLFs by activating MKP1 phosphatase. Taylor & Francis 2021-05-23 /pmc/articles/PMC8806876/ /pubmed/34024253 http://dx.doi.org/10.1080/21655979.2021.1928930 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Liu, Di
Du, Juan
Sun, Jing
Li, Minqi
Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase
title Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase
title_full Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase
title_fullStr Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase
title_full_unstemmed Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase
title_short Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase
title_sort parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating mkp1 phosphatase
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806876/
https://www.ncbi.nlm.nih.gov/pubmed/34024253
http://dx.doi.org/10.1080/21655979.2021.1928930
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