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Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect
Background: Medication-related osteonecrosis of the jaw is a serious complication that develops in oncologic patients treated with Zoledronic acid. Although used for over 30 years, the influence of Zoledronic acid on bone has been thoroughly investigated, mainly on osteoclasts. While decreasing oste...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450747/ https://www.ncbi.nlm.nih.gov/pubmed/37637413 http://dx.doi.org/10.3389/fphar.2023.1172705 |
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author | Berg, Tal Doppelt-Flikshtain, Ofri Coyac, Benjamin R. Zigdon-Giladi, Hadar |
author_facet | Berg, Tal Doppelt-Flikshtain, Ofri Coyac, Benjamin R. Zigdon-Giladi, Hadar |
author_sort | Berg, Tal |
collection | PubMed |
description | Background: Medication-related osteonecrosis of the jaw is a serious complication that develops in oncologic patients treated with Zoledronic acid. Although used for over 30 years, the influence of Zoledronic acid on bone has been thoroughly investigated, mainly on osteoclasts. While decreasing osteoclast differentiation and function, for many years it was thought that Zoledronic acid increased osteoblast differentiation, thus increasing bone volume. Moreover, despite the influence of soft tissue on the bone healing process, the impact of zoledronic acid on the interaction between soft tissue and bone was not investigated. Aim: Our goal was to investigate the influence of Zoledronic Acid and soft tissue cells on osteogenic differentiation of mesenchymal stem cells (MSCs). Materials and methods: Osteogenic differentiation of MSCs was examined after exposure to Zoledronic Acid. To determine the influence of soft tissue cells on MSCs’ osteogenic differentiation, conditioned media from keratinocytes and oral fibroblasts were added to osteogenic medium supplemented with Zoledronic Acid. Proteomic composition of keratinocytes’ and fibroblasts’ conditioned media were analyzed. Results: Zoledronic Acid decreased osteogenic differentiation of MSCs by seven-fold. The osteogenic differentiation of MSCs was restored by the supplementation of fibroblasts’ conditioned medium to osteogenic medium, despite Zoledronic acid treatment. Five osteogenic proteins involved in the TGFβ pathway were exclusively identified in fibroblasts’ conditioned medium, suggesting their role in the rescue effect. Conclusion: Oral fibroblasts secrete proteins that enable osteogenic differentiation of MSCs in the presence of Zoledronic Acid. |
format | Online Article Text |
id | pubmed-10450747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104507472023-08-26 Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect Berg, Tal Doppelt-Flikshtain, Ofri Coyac, Benjamin R. Zigdon-Giladi, Hadar Front Pharmacol Pharmacology Background: Medication-related osteonecrosis of the jaw is a serious complication that develops in oncologic patients treated with Zoledronic acid. Although used for over 30 years, the influence of Zoledronic acid on bone has been thoroughly investigated, mainly on osteoclasts. While decreasing osteoclast differentiation and function, for many years it was thought that Zoledronic acid increased osteoblast differentiation, thus increasing bone volume. Moreover, despite the influence of soft tissue on the bone healing process, the impact of zoledronic acid on the interaction between soft tissue and bone was not investigated. Aim: Our goal was to investigate the influence of Zoledronic Acid and soft tissue cells on osteogenic differentiation of mesenchymal stem cells (MSCs). Materials and methods: Osteogenic differentiation of MSCs was examined after exposure to Zoledronic Acid. To determine the influence of soft tissue cells on MSCs’ osteogenic differentiation, conditioned media from keratinocytes and oral fibroblasts were added to osteogenic medium supplemented with Zoledronic Acid. Proteomic composition of keratinocytes’ and fibroblasts’ conditioned media were analyzed. Results: Zoledronic Acid decreased osteogenic differentiation of MSCs by seven-fold. The osteogenic differentiation of MSCs was restored by the supplementation of fibroblasts’ conditioned medium to osteogenic medium, despite Zoledronic acid treatment. Five osteogenic proteins involved in the TGFβ pathway were exclusively identified in fibroblasts’ conditioned medium, suggesting their role in the rescue effect. Conclusion: Oral fibroblasts secrete proteins that enable osteogenic differentiation of MSCs in the presence of Zoledronic Acid. Frontiers Media S.A. 2023-08-11 /pmc/articles/PMC10450747/ /pubmed/37637413 http://dx.doi.org/10.3389/fphar.2023.1172705 Text en Copyright © 2023 Berg, Doppelt-Flikshtain, Coyac and Zigdon-Giladi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Berg, Tal Doppelt-Flikshtain, Ofri Coyac, Benjamin R. Zigdon-Giladi, Hadar Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect |
title | Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect |
title_full | Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect |
title_fullStr | Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect |
title_full_unstemmed | Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect |
title_short | Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect |
title_sort | oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to zoledronic acid in a paracrine effect |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450747/ https://www.ncbi.nlm.nih.gov/pubmed/37637413 http://dx.doi.org/10.3389/fphar.2023.1172705 |
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