Alternative Model to Animal Experiments by Reproducing the Physical Environment of Living Cartilage

抄録

Articular cartilage is a tissue exposed to various mechanical stimuli. Normal mechanical stimuli play an important role in chondrocyte activity inside the tissue by modulating extracellular matrix production, differentiation, and proliferation. However, excessive mechanical stimulation induces inflammation in cartilage, which leads to decreased expression of genes involved in chondrocyte homeostasis, accelerated degradation of the extracellular matrix, and apoptosis. Low-intensity mechanical stimulation is also used in physical therapy to promote functional tissue recovery, and the effects of mechanical stimulation on cartilage tissue are diverse. Though the effects of individual stimuli on chondrocytes have been extensively studied, the effects of combined stimuli on chondrocytes in a three-dimensional environment are still unknown. Recently, we developed a new bioreactor that could simultaneously and independently apply hydrostatic pressure and compressive strain to cells embedded in a 3D construct. In this study, we investigated the expression levels of genes involved in inflammation and osteoarthritis when compressive stress and hydrostatic pressure were applied to a 3D tissue model in which mouse chondrocytes (ATDC5 cells) were included in a 3D gel. We found that different trends were obtained between single stimulation and compound stimulation. Therefore, the simultaneous application of compressive stress and hydrostatic pressure, which was used to mimic the main mechanical environment of cartilage, is expected to greatly contribute to the elucidation of cartilage pathogenesis and homeostasis. The model developed in this study is believed to be an important tool as an alternative model for animal experiments on cartilage tissue.