A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro

• Main Authors: Alexandra Damerau, Moritz Pfeiffenberger, Marie-Christin Weber, Gerd-Rüdiger Burmester, Frank Buttgereit, Timo Gaber, Annemarie Lang
• Format: Article
• Language: English
• Published: MDPI AG 2021-12-01
• Series: International Journal of Molecular Sciences
• Subjects: mesenchymal stem cells; tissue engineering; osteochondral unit; in vitro model; rheumatoid arthritis
• Online Access: https://www.mdpi.com/1422-0067/22/1/128
• ISSN: 1661-6596; 1422-0067

Adequate tissue engineered models are required to further understand the (patho)physiological mechanism involved in the destructive processes of cartilage and subchondral bone during rheumatoid arthritis (RA). Therefore, we developed a human in vitro 3D osteochondral tissue model (OTM), mimicking cytokine-induced cellular and matrix-related changes leading to cartilage degradation and bone destruction in order to ultimately provide a preclinical drug screening tool. To this end, the OTM was engineered by co-cultivation of mesenchymal stromal cell (MSC)-derived bone and cartilage components in a 3D environment. It was comprehensively characterized on cell, protein, and mRNA level. Stimulating the OTM with proinflammatory cytokines, relevant in RA (tumor necrosis factor α, interleukin-6, macrophage migration inhibitory factor ), caused cell- and matrix-related changes, resulting in a significantly induced the gene expression of lactate dehydrogenase A, interleukin-8 and tumor necrosis factor αin both, cartilage, and bone, while the matrix metalloproteases (MMPs) <i>MMP1</i> and <i>MMP3</i> expression were only induced in cartilage. Finally, application of target-specific drugs prevented the induction of inflammation and matrix-degradation. Thus, we here provide evidence that our human in vitro 3D OTM mimics cytokine-induced cell- and matrix-related changes—key features of RA—and may serve as a preclinical tool for the evaluation of both new targets and potential drugs in a more translational setup.