Proton and Carbon Ion Irradiation Changes the Process of Endochondral Ossification in an Ex Vivo Femur Organotypic Culture Model
Particle therapy (PT) that utilizes protons and carbon ions offers a promising way to reduce the side effects of radiation oncology, especially in pediatric patients. To investigate the influence of PT on growing bone, we exposed an organotypic rat ex vivo femur culture model to PT. After irradiatio...
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MDPI AG
2023-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/18/2301 |
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| author | Vanessa Etschmaier Dietmar Glänzer Nicole Eck Ute Schäfer Andreas Leithner Dietmar Georg Birgit Lohberger |
| author_facet | Vanessa Etschmaier Dietmar Glänzer Nicole Eck Ute Schäfer Andreas Leithner Dietmar Georg Birgit Lohberger |
| author_sort | Vanessa Etschmaier |
| collection | DOAJ |
| description | Particle therapy (PT) that utilizes protons and carbon ions offers a promising way to reduce the side effects of radiation oncology, especially in pediatric patients. To investigate the influence of PT on growing bone, we exposed an organotypic rat ex vivo femur culture model to PT. After irradiation, histological staining, immunohistochemical staining, and gene expression analysis were conducted following 1 or 14 days of in vitro culture (DIV). Our data indicated a significant loss of proliferating chondrocytes at 1 DIV, which was followed by regeneration attempts through chondrocytic cluster formation at 14 DIV. Accelerated levels of mineralization were observed, which correlated with increased proteoglycan production and secretion into the pericellular matrix. Col2α1 expression, which increased during the cultivation period, was significantly inhibited by PT. Additionally, the decrease in ColX expression over time was more pronounced compared to the non-IR control. The chondrogenic markers BMP2, RUNX2, OPG, and the osteogenic marker ALPL, showed a significant reduction in the increase in expression after 14 DIV due to PT treatment. It was noted that carbon ions had a stronger influence than protons. Our bone model demonstrated the occurrence of pathological and regenerative processes induced by PT, thus building on the current understanding of the biological mechanisms of bone. |
| first_indexed | 2024-03-10T22:56:11Z |
| format | Article |
| id | doaj.art-4a460cc946e448699b118acc4e98108f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T22:56:11Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-4a460cc946e448699b118acc4e98108f2023-11-19T10:00:07ZengMDPI AGCells2073-44092023-09-011218230110.3390/cells12182301Proton and Carbon Ion Irradiation Changes the Process of Endochondral Ossification in an Ex Vivo Femur Organotypic Culture ModelVanessa Etschmaier0Dietmar Glänzer1Nicole Eck2Ute Schäfer3Andreas Leithner4Dietmar Georg5Birgit Lohberger6Department of Orthopaedics and Trauma, Medical University Graz, 8036 Graz, AustriaDepartment of Orthopaedics and Trauma, Medical University Graz, 8036 Graz, AustriaDepartment of Orthopaedics and Trauma, Medical University Graz, 8036 Graz, AustriaDepartment of Neurosurgery, Research Unit for Experimental Neurotraumatology, Medical University of Graz, 8036 Graz, AustriaDepartment of Orthopaedics and Trauma, Medical University Graz, 8036 Graz, AustriaDepartment of Radiation Oncology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Orthopaedics and Trauma, Medical University Graz, 8036 Graz, AustriaParticle therapy (PT) that utilizes protons and carbon ions offers a promising way to reduce the side effects of radiation oncology, especially in pediatric patients. To investigate the influence of PT on growing bone, we exposed an organotypic rat ex vivo femur culture model to PT. After irradiation, histological staining, immunohistochemical staining, and gene expression analysis were conducted following 1 or 14 days of in vitro culture (DIV). Our data indicated a significant loss of proliferating chondrocytes at 1 DIV, which was followed by regeneration attempts through chondrocytic cluster formation at 14 DIV. Accelerated levels of mineralization were observed, which correlated with increased proteoglycan production and secretion into the pericellular matrix. Col2α1 expression, which increased during the cultivation period, was significantly inhibited by PT. Additionally, the decrease in ColX expression over time was more pronounced compared to the non-IR control. The chondrogenic markers BMP2, RUNX2, OPG, and the osteogenic marker ALPL, showed a significant reduction in the increase in expression after 14 DIV due to PT treatment. It was noted that carbon ions had a stronger influence than protons. Our bone model demonstrated the occurrence of pathological and regenerative processes induced by PT, thus building on the current understanding of the biological mechanisms of bone.https://www.mdpi.com/2073-4409/12/18/2301organotypic bone slidesparticle therapyproton irradiationcarbon ion irradiationbone biology |
| spellingShingle | Vanessa Etschmaier Dietmar Glänzer Nicole Eck Ute Schäfer Andreas Leithner Dietmar Georg Birgit Lohberger Proton and Carbon Ion Irradiation Changes the Process of Endochondral Ossification in an Ex Vivo Femur Organotypic Culture Model Cells organotypic bone slides particle therapy proton irradiation carbon ion irradiation bone biology |
| title | Proton and Carbon Ion Irradiation Changes the Process of Endochondral Ossification in an Ex Vivo Femur Organotypic Culture Model |
| title_full | Proton and Carbon Ion Irradiation Changes the Process of Endochondral Ossification in an Ex Vivo Femur Organotypic Culture Model |
| title_fullStr | Proton and Carbon Ion Irradiation Changes the Process of Endochondral Ossification in an Ex Vivo Femur Organotypic Culture Model |
| title_full_unstemmed | Proton and Carbon Ion Irradiation Changes the Process of Endochondral Ossification in an Ex Vivo Femur Organotypic Culture Model |
| title_short | Proton and Carbon Ion Irradiation Changes the Process of Endochondral Ossification in an Ex Vivo Femur Organotypic Culture Model |
| title_sort | proton and carbon ion irradiation changes the process of endochondral ossification in an ex vivo femur organotypic culture model |
| topic | organotypic bone slides particle therapy proton irradiation carbon ion irradiation bone biology |
| url | https://www.mdpi.com/2073-4409/12/18/2301 |
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