Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro

Abstract Radiotherapy of head and neck squamous cell carcinoma can lead to long-term complications like osteoradionecrosis, resulting in severe impairment of the jawbone. Current standard procedures require a 6-month wait after irradiation before dental reconstruction can begin. A comprehensive char...

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Autores principales:	Anna-Klara Amler, Domenic Schlauch, Selin Tüzüner, Alexander Thomas, Norbert Neckel, Ingeborg Tinhofer, Max Heiland, Roland Lauster, Lutz Kloke, Carmen Stromberger, Susanne Nahles
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4796e467585e46808a71b4d930f1e3f5
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spelling	oai:doaj.org-article:4796e467585e46808a71b4d930f1e3f52021-12-02T19:16:11ZPilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro10.1038/s41598-021-99323-82045-2322https://doaj.org/article/4796e467585e46808a71b4d930f1e3f52021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99323-8https://doaj.org/toc/2045-2322Abstract Radiotherapy of head and neck squamous cell carcinoma can lead to long-term complications like osteoradionecrosis, resulting in severe impairment of the jawbone. Current standard procedures require a 6-month wait after irradiation before dental reconstruction can begin. A comprehensive characterization of the irradiation-induced molecular and functional changes in bone cells could allow the development of novel strategies for an earlier successful dental reconstruction in patients treated by radiotherapy. The impact of ionizing radiation on the bone-forming alveolar osteoblasts remains however elusive, as previous studies have relied on animal-based models and fetal or animal-derived cell lines. This study presents the first in vitro data obtained from primary human alveolar osteoblasts. Primary human alveolar osteoblasts were isolated from healthy donors and expanded. After X-ray irradiation with 2, 6 and 10 Gy, cells were cultivated under osteogenic conditions and analyzed regarding their proliferation, mineralization, and expression of marker genes and proteins. Proliferation of osteoblasts decreased in a dose-dependent manner. While cells recovered from irradiation with 2 Gy, application of 6 and 10 Gy doses not only led to a permanent impairment of proliferation, but also resulted in altered cell morphology and a disturbed structure of the extracellular matrix as demonstrated by immunostaining of collagen I and fibronectin. Following irradiation with any of the examined doses, a decrease of marker gene expression levels was observed for most of the investigated genes, revealing interindividual differences. Primary human alveolar osteoblasts presented a considerably changed phenotype after irradiation, depending on the dose administered. Mechanisms for these findings need to be further investigated. This could facilitate improved patient care by re-evaluating current standard procedures and investigating faster and safer reconstruction concepts, thus improving quality of life and social integrity.Anna-Klara AmlerDomenic SchlauchSelin TüzünerAlexander ThomasNorbert NeckelIngeborg TinhoferMax HeilandRoland LausterLutz KlokeCarmen StrombergerSusanne NahlesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna-Klara Amler Domenic Schlauch Selin Tüzüner Alexander Thomas Norbert Neckel Ingeborg Tinhofer Max Heiland Roland Lauster Lutz Kloke Carmen Stromberger Susanne Nahles Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro
description	Abstract Radiotherapy of head and neck squamous cell carcinoma can lead to long-term complications like osteoradionecrosis, resulting in severe impairment of the jawbone. Current standard procedures require a 6-month wait after irradiation before dental reconstruction can begin. A comprehensive characterization of the irradiation-induced molecular and functional changes in bone cells could allow the development of novel strategies for an earlier successful dental reconstruction in patients treated by radiotherapy. The impact of ionizing radiation on the bone-forming alveolar osteoblasts remains however elusive, as previous studies have relied on animal-based models and fetal or animal-derived cell lines. This study presents the first in vitro data obtained from primary human alveolar osteoblasts. Primary human alveolar osteoblasts were isolated from healthy donors and expanded. After X-ray irradiation with 2, 6 and 10 Gy, cells were cultivated under osteogenic conditions and analyzed regarding their proliferation, mineralization, and expression of marker genes and proteins. Proliferation of osteoblasts decreased in a dose-dependent manner. While cells recovered from irradiation with 2 Gy, application of 6 and 10 Gy doses not only led to a permanent impairment of proliferation, but also resulted in altered cell morphology and a disturbed structure of the extracellular matrix as demonstrated by immunostaining of collagen I and fibronectin. Following irradiation with any of the examined doses, a decrease of marker gene expression levels was observed for most of the investigated genes, revealing interindividual differences. Primary human alveolar osteoblasts presented a considerably changed phenotype after irradiation, depending on the dose administered. Mechanisms for these findings need to be further investigated. This could facilitate improved patient care by re-evaluating current standard procedures and investigating faster and safer reconstruction concepts, thus improving quality of life and social integrity.
format	article
author	Anna-Klara Amler Domenic Schlauch Selin Tüzüner Alexander Thomas Norbert Neckel Ingeborg Tinhofer Max Heiland Roland Lauster Lutz Kloke Carmen Stromberger Susanne Nahles
author_facet	Anna-Klara Amler Domenic Schlauch Selin Tüzüner Alexander Thomas Norbert Neckel Ingeborg Tinhofer Max Heiland Roland Lauster Lutz Kloke Carmen Stromberger Susanne Nahles
author_sort	Anna-Klara Amler
title	Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro
title_short	Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro
title_full	Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro
title_fullStr	Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro
title_full_unstemmed	Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro
title_sort	pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4796e467585e46808a71b4d930f1e3f5
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Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro

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