RESUMEN
Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2022;11(5):292-300.
RESUMEN
Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2021;10(2):122-133.
RESUMEN
Accumulation of advanced glycation end products (AGEs) in the articular cartilage is a major risk factor for osteoarthritis (OA). To determine the mechanistic basis of AGE action in OA, we treated human articular chondrocytes with AGEs, and found that they not only up-regulated the pro-inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, but also inhibited AMP-activated protein kinase (AMPK) phosphorylation and decreased sirtuin 1 (SIRT-1) levels in a concentration- and time-dependent manner. Pioglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) agonist restored the inhibited AMPK and SIRT-1 by AGEs. Pre-treatment of the cells with the agonists or antagonists of AMPK and SIRT-1 respectively abolished and augmented the inflammatory state induced by AGEs. Furthermore, AMPK agonist also restored the levels of SIRT-1 in the AGE-stimulated chondrocytes. Our findings indicate AGEs induce an inflammatory response in human articular chondrocytes via the PPARγ/AMPK/SIRT-1 pathway, which is therefore a potential target in OA therapy.