Jinlei Li, Weitong Liu, Tao Wang, Yanbo Wang, Guang Yang, Jiankun Chen, Yongsheng Xu, Jingfan Yang
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引用次数: 0
Abstract
A core role of chondrocyte survival/death has been suggested in the pathogenesis of osteoarthritis. We explored the underlying molecular mechanism of curcumin protecting against interleukin-1β (IL-1β)-induced chondrocyte injury via the bone morphogenetic protein 2 (Bmp2)/small mothers against decapentaplegic homolog 5 (Smad5)/runt-related transcription factor 2 (Runx2) pathway. Chondrocytes ATDC5 in vitro inflammatory model was established by IL-1β induction, and treated with curcumin, or Smad5 small interfering RNA. Levels of extracellular matrix (ECM) type II collagen (Col-II) and aggrecan, reactive oxygen species (ROS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and IL-6 were determined by immunocytochemistry, kits and ELISA. Apoptosis and necrosis were assessed by Annexin V/PI and TUNEL. Matrix metalloproteinase 13 (MMP13), A disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5), Bmp2/Smad5/Runx2 expression and Smad5 phosphorylation levels were determined by qPCR and western blot. IL-1β-treated ATDC5 cells showed decreased Col-II, aggrecan in ECM and SOD and GSH-Px levels, as well as increased apoptosis and levels of MMP13, ADAMTS5, Bmp2, Runx2, ROS, COX-2, TNF-α and IL-6 and Smad5 phosphorylation (all p < 0.05), whilst curcumin treatment brought about the opposite trends, suggesting that curcumin inhibited oxidative stress, inflammatory response and apoptosis, and inactivated the Bmp2/Smad5/Runx2 pathway in IL-1β-treated chondrocytes. Additionally, Smad5 silencing also caused suppressed oxidative stress, inflammatory response and apoptosis in IL-1β-treated chondrocytes. Curcumin reduced IL-1β-induced chondrocyte oxidative stress, inflammation, and apoptosis, and increased ECM secretion by inactivating the Bmp2/Smad5/Runx2 pathway, thereby exerting a protective effect on injured chondrocytes.
期刊介绍：
The scope of the Journal includes:
1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products.
2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools.
3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research.
4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy.
5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.
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