Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells

Pirosa, Alessandro; Tankus, Esma Bahar; Mainardi, Andrea; Occhetta, Paola; Dönges, Laura; Baum, Cornelia; Rasponi, Marco; Martin, Ivan; Barbero, Andrea

doi:10.3390/ijms22179581

Open AccessArticle

Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells

by

Alessandro Pirosa

¹,

Esma Bahar Tankus

^1,†,

Andrea Mainardi

^1,2,3,†

,

Paola Occhetta

²

,

Laura Dönges

¹,

Cornelia Baum

^4,5,

Marco Rasponi

²

,

Ivan Martin

¹

and

Andrea Barbero

^1,*

¹

Department of Biomedicine, University Hospital Basel, University of Basel, 4056 Basel, Switzerland

²

Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy

³

Department of Biomedical Engineering, University of Basel, 4123 Allschwil, Switzerland

⁴

Department of Orthopaedic Surgery and Traumatology, University Hospital Basel, 4031 Basel, Switzerland

⁵

Department of Research and Development, Schulthess Klinik Zurich, 8008 Zurich, Switzerland

^*

Author to whom correspondence should be addressed.

^†

Equally contributing authors.

Int. J. Mol. Sci. 2021, 22(17), 9581; https://doi.org/10.3390/ijms22179581

Submission received: 1 July 2021 / Revised: 25 August 2021 / Accepted: 1 September 2021 / Published: 3 September 2021

(This article belongs to the Special Issue Osteoblast Differentiation and Activity in Skeletal Diseases)

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Abstract

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.

Keywords: osteoarthritis; mesenchymal stromal cells; endothelial cells; inflammation; photocrosslinked; gelatin

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MDPI and ACS Style

Pirosa, A.; Tankus, E.B.; Mainardi, A.; Occhetta, P.; Dönges, L.; Baum, C.; Rasponi, M.; Martin, I.; Barbero, A. Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells. Int. J. Mol. Sci. 2021, 22, 9581. https://doi.org/10.3390/ijms22179581

AMA Style

Pirosa A, Tankus EB, Mainardi A, Occhetta P, Dönges L, Baum C, Rasponi M, Martin I, Barbero A. 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. 2021; 22(17):9581. https://doi.org/10.3390/ijms22179581

Chicago/Turabian Style

Pirosa, Alessandro, Esma Bahar Tankus, Andrea Mainardi, Paola Occhetta, Laura Dönges, Cornelia Baum, Marco Rasponi, Ivan Martin, and Andrea Barbero. 2021. "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 22, no. 17: 9581. https://doi.org/10.3390/ijms22179581

APA Style

Pirosa, A., Tankus, E. B., Mainardi, A., Occhetta, P., Dönges, L., Baum, C., Rasponi, M., Martin, I., & Barbero, A. (2021). 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, 22(17), 9581. https://doi.org/10.3390/ijms22179581

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Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells

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