RANKL neutralisation prevents osteoclast activation in a human ameloblastoma-bone model
Ameloblastoma is a benign, locally invasive epithelial odontogenic neoplasm of the jaw. Treatment of choice is jaw resection, often resulting in significant morbidity. The aim of this study was to recapitulate ameloblastoma in a completely humanised 3D disease model containing ameloblastoma cells, o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-12-01
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| Series: | Journal of Tissue Engineering |
| Online Access: | https://doi.org/10.1177/20417314221140500 |
| _version_ | 1797977786923614208 |
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| author | Judith Pape Deniz Bakkalci Rawiya Al Hosni Benjamin S Simpson Kristiina Heikinheimo Stefano Fedele Umber Cheema |
| author_facet | Judith Pape Deniz Bakkalci Rawiya Al Hosni Benjamin S Simpson Kristiina Heikinheimo Stefano Fedele Umber Cheema |
| author_sort | Judith Pape |
| collection | DOAJ |
| description | Ameloblastoma is a benign, locally invasive epithelial odontogenic neoplasm of the jaw. Treatment of choice is jaw resection, often resulting in significant morbidity. The aim of this study was to recapitulate ameloblastoma in a completely humanised 3D disease model containing ameloblastoma cells, osteoblasts and activated osteoclasts to investigate the RANKL pathway within the ameloblastoma stromal environment and its response to the RANKL antibody denosumab. In vitro bone was engineered by culturing human osteoblasts (hOB) in a biomimetic, dense collagen type I matrix, resulting in extensive mineral deposits by day 21 forming alizarin red positive bone like nodules throughout the 3D model. Activated TRAP + human osteoclasts were confirmed through the differentiation of human CD14+ monocytes after 10 days within the model. Lastly, the ameloblastoma cell lines AM-1 and AM-3 were incorporated into the 3D model. RANKL release was validated through TACE/ADAM17 activation chemically or through hOB co-culture. Denosumab treatment resulted in decreased osteoclast activation in the presence of hOB and ameloblastoma cells. These findings stress the importance of accurately modelling tumour and stromal populations as a preclinical testing platform. |
| first_indexed | 2024-04-11T05:12:35Z |
| format | Article |
| id | doaj.art-0912d38704924aa687d75d318345cf66 |
| institution | Directory Open Access Journal |
| issn | 2041-7314 |
| language | English |
| last_indexed | 2024-04-11T05:12:35Z |
| publishDate | 2022-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Tissue Engineering |
| spelling | doaj.art-0912d38704924aa687d75d318345cf662022-12-24T15:03:28ZengSAGE PublishingJournal of Tissue Engineering2041-73142022-12-011310.1177/20417314221140500RANKL neutralisation prevents osteoclast activation in a human ameloblastoma-bone modelJudith Pape0Deniz Bakkalci1Rawiya Al Hosni2Benjamin S Simpson3Kristiina Heikinheimo4Stefano Fedele5Umber Cheema6UCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, London, UKUCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, London, UKUCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, London, UKResearch Department of Targeted Intervention, Division of Surgery and Interventional Science, University College London, London, UKDepartment of Oral and Maxillofacial Surgery, Institute of Dentistry, University of Turku and Turku University Hospital, Turku, FinlandEastman Dental Institute, Oral Medicine Unit, University College London, London, UKUCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, London, UKAmeloblastoma is a benign, locally invasive epithelial odontogenic neoplasm of the jaw. Treatment of choice is jaw resection, often resulting in significant morbidity. The aim of this study was to recapitulate ameloblastoma in a completely humanised 3D disease model containing ameloblastoma cells, osteoblasts and activated osteoclasts to investigate the RANKL pathway within the ameloblastoma stromal environment and its response to the RANKL antibody denosumab. In vitro bone was engineered by culturing human osteoblasts (hOB) in a biomimetic, dense collagen type I matrix, resulting in extensive mineral deposits by day 21 forming alizarin red positive bone like nodules throughout the 3D model. Activated TRAP + human osteoclasts were confirmed through the differentiation of human CD14+ monocytes after 10 days within the model. Lastly, the ameloblastoma cell lines AM-1 and AM-3 were incorporated into the 3D model. RANKL release was validated through TACE/ADAM17 activation chemically or through hOB co-culture. Denosumab treatment resulted in decreased osteoclast activation in the presence of hOB and ameloblastoma cells. These findings stress the importance of accurately modelling tumour and stromal populations as a preclinical testing platform.https://doi.org/10.1177/20417314221140500 |
| spellingShingle | Judith Pape Deniz Bakkalci Rawiya Al Hosni Benjamin S Simpson Kristiina Heikinheimo Stefano Fedele Umber Cheema RANKL neutralisation prevents osteoclast activation in a human ameloblastoma-bone model Journal of Tissue Engineering |
| title | RANKL neutralisation prevents osteoclast activation in a human ameloblastoma-bone model |
| title_full | RANKL neutralisation prevents osteoclast activation in a human ameloblastoma-bone model |
| title_fullStr | RANKL neutralisation prevents osteoclast activation in a human ameloblastoma-bone model |
| title_full_unstemmed | RANKL neutralisation prevents osteoclast activation in a human ameloblastoma-bone model |
| title_short | RANKL neutralisation prevents osteoclast activation in a human ameloblastoma-bone model |
| title_sort | rankl neutralisation prevents osteoclast activation in a human ameloblastoma bone model |
| url | https://doi.org/10.1177/20417314221140500 |
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