Damerau Alexandra, Nguyen Duc Ha Do, Lubahn Christina, Renggli Kasper, Pfeiffenberger Moritz, Krönke Gerhard, Herrmann Matthias, Leeuw Thomas, Buttgereit Frank, Gaber Timo
Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.
German Rheumatism Research Centre (DRFZ) Berlin, a Leibniz Institute, 10117, Berlin, Germany.
Adv Sci (Weinh). 2025 Feb;12(7):e2412010. doi: 10.1002/advs.202412010. Epub 2024 Dec 24.
Osteoarthritis (OA) is a leading cause of disability, often resulting from overuse or injury, but inactivity can also contribute to cartilage degeneration. Conventional in vivo models struggle to isolate and study the specific effects of mechanical stress on cartilage health. To address this limitation, a microphysiological system (MPS) is established to examine how varying levels of shear stress impact cartilage homeostasis. The system allows for the cultivation of 3D chondrogenic microconstructs (CMCs) derived from human mesenchymal stromal cells, simulating both physiological and pathophysiological shear stress. Inflammation is induced via TNF-α or activated peripheral blood mononuclear cells to model cartilage damage, enabling the evaluation of therapeutic interventions. The study demonstrates the development of an arthritis-like phenotype and successful restoration of cartilage conditions through a JAK inhibitor under physiological shear stress. Physiological shear stress is identified as a critical factor in maintaining cartilage integrity. This MPS offers a standardized method to study shear stress, replicate cytokine-induced cartilage damage, and simulate key features of arthritis, providing a valuable alternative to animal models.
骨关节炎（OA）是导致残疾的主要原因，通常由过度使用或损伤引起，但缺乏运动也会导致软骨退变。传统的体内模型难以分离和研究机械应力对软骨健康的具体影响。为了解决这一局限性，建立了一种微生理系统（MPS）来研究不同水平的剪切应力如何影响软骨稳态。该系统能够培养源自人间充质基质细胞的3D软骨生成微构建体（CMC），模拟生理和病理生理剪切应力。通过肿瘤坏死因子-α（TNF-α）或活化的外周血单核细胞诱导炎症以模拟软骨损伤，从而能够评估治疗干预措施。该研究表明，在生理剪切应力下，通过一种JAK抑制剂可出现类似关节炎的表型，并成功恢复软骨状况。生理剪切应力被确定为维持软骨完整性的关键因素。这种MPS提供了一种标准化方法来研究剪切应力、复制细胞因子诱导的软骨损伤以及模拟关节炎的关键特征，为动物模型提供了有价值的替代方案。
