School of Mechanical Engineering, Yonsei University, 50 Yonsei-ro, Seadaemun-gu, Seoul 03722, Republic of Korea.
College of Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyangsi, Gyeonggi-do 10326, Republic of Korea.
Biofabrication. 2024 Aug 14;16(4). doi: 10.1088/1758-5090/ad6cf9.
Osteoporosis is the most common bone disorder, which is a highly dangerous condition that can promote bone metastases. As the current treatment for osteoporosis involves long-term medication therapy and a cure for bone metastasis is not known, ongoing efforts are required for drug development for osteoporosis. Animal experiments, traditionally used for drug development, raise ethical concerns and are expensive and time-consuming. Organ-on-a-chip technology is being developed as a tool to supplement such animal models. In this study, we developed a bone-on-a-chip by co-culturing osteoblasts, osteocytes, and osteoclasts in an extracellular matrix environment that can represent normal bone, osteopenia, and osteoporotic conditions. We then simulated bone metastases using breast cancer cells in three different bone conditions and observed that bone metastases were most active in osteoporotic conditions. Furthermore, it was revealed that the promotion of bone metastasis in osteoporotic conditions is due to increased vascular permeability. The bone-on-a-chip developed in this study can serve as a platform to complement animal models for drug development for osteoporosis and bone metastasis.
骨质疏松症是最常见的骨骼疾病，是一种非常危险的状况，可促进骨骼转移。由于目前骨质疏松症的治疗涉及长期药物治疗，而且尚未找到治疗骨骼转移的方法，因此需要继续努力开发骨质疏松症药物。传统上用于药物开发的动物实验引起了伦理问题，而且既昂贵又耗时。正在开发器官芯片技术作为补充此类动物模型的工具。在这项研究中，我们通过在可以代表正常骨骼、低骨量和骨质疏松症状况的细胞外基质环境中共同培养成骨细胞、骨细胞和破骨细胞，开发了一种骨芯片。然后，我们在三种不同的骨骼条件下使用乳腺癌细胞模拟骨骼转移，并观察到在骨质疏松症条件下骨骼转移最为活跃。此外，研究揭示了骨质疏松症条件下促进骨骼转移是由于血管通透性增加所致。本研究中开发的骨芯片可以作为一个平台，补充用于骨质疏松症和骨骼转移药物开发的动物模型。
