Department of Exercise Health Science, National Taiwan University of Sport, Taichung 404393, Taiwan.
School of Medicine, China Medical University, Taichung 404022, Taiwan.
Cells. 2020 Apr 10;9(4):927. doi: 10.3390/cells9040927.
Osteoarthritis (OA) is a chronic inflammatory and progressive joint disease that results in cartilage degradation and subchondral bone remodeling. The proinflammatory cytokine interleukin 1 beta (IL-1β) is abundantly expressed in OA and plays a crucial role in cartilage remodeling, although its role in the activity of chondrocytes in cartilage and subchondral remodeling remains unclear. In this study, stimulating chondrogenic ATDC5 cells with IL-1β increased the levels of bone morphogenetic protein 2 (BMP-2), promoted articular cartilage degradation, and enhanced structural remodeling. Immunohistochemistry staining and microcomputed tomography imaging of the subchondral trabecular bone region in the experimental OA rat model revealed that the OA disease promotes levels of IL-1β, BMP-2, and matrix metalloproteinase 13 (MMP-13) expression in the articular cartilage and enhances subchondral bone remodeling. The intra-articular injection of Noggin protein (a BMP-2 inhibitor) attenuated subchondral bone remodeling and disease progression in OA rats. We also found that IL-1β increased BMP-2 expression by activating the mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK), and specificity protein 1 (Sp1) signaling pathways. We conclude that IL-1β promotes BMP-2 expression in chondrocytes via the MEK/ERK/Sp1 signaling pathways. The administration of Noggin protein reduces the expression of IL-1β and BMP-2, which prevents cartilage degeneration and OA development.
骨关节炎（OA）是一种慢性炎症性和进行性关节疾病，导致软骨降解和软骨下骨重塑。促炎性细胞因子白细胞介素 1β（IL-1β）在 OA 中大量表达，在软骨重塑中起关键作用，尽管其在软骨和软骨下重塑中软骨细胞活性中的作用仍不清楚。在这项研究中，用 IL-1β刺激软骨形成的 ATDC5 细胞增加骨形态发生蛋白 2（BMP-2）的水平，促进关节软骨降解，并增强结构重塑。实验性 OA 大鼠模型的软骨下骨小梁区域的免疫组织化学染色和微计算机断层扫描成像显示，OA 疾病促进关节软骨中 IL-1β、BMP-2 和基质金属蛋白酶 13（MMP-13）的表达，并增强软骨下骨重塑。关节内注射 Noggin 蛋白（BMP-2 抑制剂）可减轻 OA 大鼠的软骨下骨重塑和疾病进展。我们还发现，IL-1β通过激活丝裂原活化蛋白激酶（MEK）、细胞外信号调节激酶（ERK）和特异性蛋白 1（Sp1）信号通路增加 BMP-2 的表达。我们得出结论，IL-1β通过 MEK/ERK/Sp1 信号通路促进软骨细胞中 BMP-2 的表达。Noggin 蛋白的给药减少了 IL-1β和 BMP-2 的表达，从而防止软骨退化和 OA 发展。
