Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells
The subchondral bone and its associated vasculature play an important role in the onset of osteoarthritis (OA). Integration of different aspects of the OA environment into multi-cellular and complex human, in vitro models is therefore needed to properly represent the pathology. In this study, we exp...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9581 |
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| author | Alessandro Pirosa Esma Bahar Tankus Andrea Mainardi Paola Occhetta Laura Dönges Cornelia Baum Marco Rasponi Ivan Martin Andrea Barbero |
| author_facet | Alessandro Pirosa Esma Bahar Tankus Andrea Mainardi Paola Occhetta Laura Dönges Cornelia Baum Marco Rasponi Ivan Martin Andrea Barbero |
| author_sort | Alessandro Pirosa |
| collection | DOAJ |
| description | The subchondral bone and its associated vasculature play an important role in the onset of osteoarthritis (OA). Integration of different aspects of the OA environment into multi-cellular and complex human, in vitro models is therefore needed to properly represent the pathology. In this study, we exploited a mesenchymal stromal cell line/endothelial cell co-culture to produce an in vitro human model of vascularized osteogenic tissue. A cocktail of inflammatory cytokines, or conditioned medium from mechanically-induced OA engineered microcartilage, was administered to this vascularized bone model to mimic the inflamed OA environment, hypothesizing that these treatments could induce the onset of specific pathological traits. Exposure to the inflammatory factors led to increased network formation by endothelial cells, reminiscent of the abnormal angiogenesis found in OA subchondral bone, demineralization of the constructs, and increased collagen production, signs of OA related bone sclerosis. Furthermore, inflammation led to augmented expression of osteogenic (alkaline phosphatase (ALP) and osteocalcin (OCN)) and angiogenic (vascular endothelial growth factor (VEGF)) genes. The treatment, with a conditioned medium from the mechanically-induced OA engineered microcartilage, also caused increased demineralization and expression of ALP, OCN, ADAMTS5, and VEGF; however, changes in network formation by endothelial cells were not observed in this second case, suggesting a possible different mechanism of action in inducing OA-like phenotypes. We propose that this vascularized bone model could represent a first step for the in vitro study of bone changes under OA mimicking conditions and possibly serve as a tool in testing anti-OA drugs. |
| first_indexed | 2024-03-10T08:09:24Z |
| format | Article |
| id | doaj.art-0384908fe1f64cbd82b40de1f5644a2f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:09:24Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0384908fe1f64cbd82b40de1f5644a2f2023-11-22T10:45:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012217958110.3390/ijms22179581Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial CellsAlessandro Pirosa0Esma Bahar Tankus1Andrea Mainardi2Paola Occhetta3Laura Dönges4Cornelia Baum5Marco Rasponi6Ivan Martin7Andrea Barbero8Department of Biomedicine, University Hospital Basel, University of Basel, 4056 Basel, SwitzerlandDepartment of Biomedicine, University Hospital Basel, University of Basel, 4056 Basel, SwitzerlandDepartment of Biomedicine, University Hospital Basel, University of Basel, 4056 Basel, SwitzerlandDepartment of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, ItalyDepartment of Biomedicine, University Hospital Basel, University of Basel, 4056 Basel, SwitzerlandDepartment of Orthopaedic Surgery and Traumatology, University Hospital Basel, 4031 Basel, SwitzerlandDepartment of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, ItalyDepartment of Biomedicine, University Hospital Basel, University of Basel, 4056 Basel, SwitzerlandDepartment of Biomedicine, University Hospital Basel, University of Basel, 4056 Basel, SwitzerlandThe subchondral bone and its associated vasculature play an important role in the onset of osteoarthritis (OA). Integration of different aspects of the OA environment into multi-cellular and complex human, in vitro models is therefore needed to properly represent the pathology. In this study, we exploited a mesenchymal stromal cell line/endothelial cell co-culture to produce an in vitro human model of vascularized osteogenic tissue. A cocktail of inflammatory cytokines, or conditioned medium from mechanically-induced OA engineered microcartilage, was administered to this vascularized bone model to mimic the inflamed OA environment, hypothesizing that these treatments could induce the onset of specific pathological traits. Exposure to the inflammatory factors led to increased network formation by endothelial cells, reminiscent of the abnormal angiogenesis found in OA subchondral bone, demineralization of the constructs, and increased collagen production, signs of OA related bone sclerosis. Furthermore, inflammation led to augmented expression of osteogenic (alkaline phosphatase (ALP) and osteocalcin (OCN)) and angiogenic (vascular endothelial growth factor (VEGF)) genes. The treatment, with a conditioned medium from the mechanically-induced OA engineered microcartilage, also caused increased demineralization and expression of ALP, OCN, ADAMTS5, and VEGF; however, changes in network formation by endothelial cells were not observed in this second case, suggesting a possible different mechanism of action in inducing OA-like phenotypes. We propose that this vascularized bone model could represent a first step for the in vitro study of bone changes under OA mimicking conditions and possibly serve as a tool in testing anti-OA drugs.https://www.mdpi.com/1422-0067/22/17/9581osteoarthritismesenchymal stromal cellsendothelial cellsinflammationphotocrosslinkedgelatin |
| spellingShingle | Alessandro Pirosa Esma Bahar Tankus Andrea Mainardi Paola Occhetta Laura Dönges Cornelia Baum Marco Rasponi Ivan Martin Andrea Barbero Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells International Journal of Molecular Sciences osteoarthritis mesenchymal stromal cells endothelial cells inflammation photocrosslinked gelatin |
| title | Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells |
| title_full | Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells |
| title_fullStr | Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells |
| title_full_unstemmed | Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells |
| title_short | Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells |
| title_sort | modeling in vitro osteoarthritis phenotypes in a vascularized bone model based on a bone marrow derived mesenchymal cell line and endothelial cells |
| topic | osteoarthritis mesenchymal stromal cells endothelial cells inflammation photocrosslinked gelatin |
| url | https://www.mdpi.com/1422-0067/22/17/9581 |
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