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.
Zusammenfassung Hintergrund Die Erfassung der In-vivo-Schulterkinematik gewinnt zunehmend an Bedeutung. Fragestellung Welche neuen Methoden stehen für die In-vivo-Diagnostik der Schulterkinematik zur Verfügung? Material und Methode Es wird eine Übersicht über aktuelle Literatur und Technologien gegeben. Ergebnisse Neben der etablierten markerbasierten Bewegungsanalyse können markerlose Bewegungsanalyse, elektromagnetische Systeme, ultraschallbasierte Bewegungsanalyse, tragbare Sensoren und medizinische Bildgebung zur In-vivo-Diagnostik der Schulterkinematik verwendet werden. Jedes dieser Systeme birgt Chancen, muss aber im Kontext der jeweiligen (technischen) Vor- und Nachteile beurteilt werden. Schlussfolgerung Neue Methoden zur In-vivo-Diagnostik der Schulterkinematik erlauben die Erfassung komplexer Bewegungsmuster sowie Alltagsbewegungen und können einen direkten Bezug zur Anatomie und jeweiligen Pathologie herstellen.
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