Chloride Channel and Inflammation-Mediated Pathogenesis of Osteoarthritis

Abstract

Articular cartilage allows the human body to buffer and absorb stress during normal exercise. It is mainly composed of cartilage cells and the extracellular matrix and is surrounded by the extracellular microenvironment formed by synovial fluid and various factors in it. Studies have shown that chondrocytes are the metabolic center of articular cartilage. Under physiological conditions, the extracellular matrix is in a dynamic balance of anabolism and catabolism, and various factors and physical and chemical conditions in the extracellular microenvironment are also in a steady state. This homeostasis depends on the normal function of proteins represented by various ion channels on chondrocytes. In mammalian chondrocyte species, ion channels are mainly divided into two categories: cation channels and anion channels. Anion channels such as chloride channels have become hot research topics in recent years. These channels play an extremely important role in various physiological processes. Recently, a growing body of evidence has shown that many pathological processes, abnormal concentration of mechanical stress and chloride channel dysfunction in articular cartilage lead to microenvironment disorders, matrix and bone metabolism imbalances, which cause partial aseptic inflammation. These pathological processes initiate extracellular matrix degradation, abnormal chondrocyte death, hyperplasia of inflammatory synovium and bony. Osteoarthritis (OA) is a common clinical disease in orthopedics. Its typical manifestations are joint inflammation and pain caused by articular cartilage degeneration, but its pathogenesis has not been fully elucidated. Focusing on the physiological functions and pathological changes of chloride channels and pathophysiology of aseptic inflammation furthers the understanding of OA pathogenesis and provides possible targets for subsequent medication development.

Regulatory mechanism of circular RNA involvement in osteoarthritis

“…Articular cartilage, that consists mainly of chondrocytes surrounded by synovial fluid and ECM, allows for motion cushioning and pressure absorption (54). An accumulation of joint load, such as weight gain caused by obesity and changes in body composition, significantly increases the risk of OA (55).…”

Sprifermin for Treatment of Osteoarthritis: Recombinant Fibroblast Growth Factor 18 as a Possible Disease-Modifying Knee Osteoarthritis Drug

“…Activation of the NLRP3 (NLR family, pyrin domain containing 3; NLR, nucleotide-binding domain, leucine-rich repeat) inflammasome may also induce a distinct form of programmed lytic CD, pyroptosis [35]. Activation of distinct chloride channels and changes of intracellular ion composition appear to play an important role in this process [36]. Moreover, ferroptosis, an iron-dependent mode of cell death characterized by disturbed redox balance and lethal lipid peroxidation, and necroptosis, a caspase-independent programmed form of necrotic cell death, may play a role in the pathogenesis of OA [37].…”

Non-invasive diagnosis of bacterial and non-bacterial inflammations using a dual-enzyme-responsive fluorescent indicator

“… 2 The clinical classification of inflammation includes two main types: bacterial and non-bacterial. 3 “Bacterial inflammation” encompasses diverse inflammatory reactions elicited by bacterial infections. 4 These encompass conditions such as bacterial pneumonia, 5 bacterial arthritis, 6 bacterial gastroenteritis ( Salmonella and Escherichia coli ), 7 bacterial meningitis, 8 appendicitis caused by bacterial infection within the abdominal cavity, 9 and peritonitis.…”