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Chondrocyte ion channel function and regulation in health and disease

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Osteoarthritis research at the cell level

Osteoarthritis (OA) results in chronic deterioration of joint cartilage. Researchers have investigated the cell behind the formation of cartilage, the chondrocyte, in a bid to identify more targeted therapy for the most common cause of disability in Europe.

Fundamental Research
Health

As there is still no overall sustainable therapy for OA, there is a need to look at proteins of chondrocyte ion channels (channelome) as well as the cell’s membrane, the membranome and its surface component, the surfaceome. Essential for chondrocyte function and survival, correlating changes in ion channel expression and function during OA development could lead to a better understanding of control mechanisms and identification of biomarkers for the disease. The CHONDRION (Chondrocyte ion channel function and regulation in health and disease) project used transcriptomics, proteomics, bioinformatics and live cell electrophysiology to better characterise the membranome of healthy and osteoarthritic progenitor cells involved in OA development. Researchers optimised methods to enrich cell surface molecules, and a modified cell surface protein isolation technique localised almost 80 % of identified proteins to the surface compared with 30 % using other separation methods. Data collection is still underway and analysis promises to identify new biomarkers for OA disease development. Comparing ion channels messenger RNA expression of diseased and healthy cells, more than 100 genes were identified. The most obvious was found in a specific calcium-dependent potassium channel, and CHONDRION confirmed that the expression pattern was evident at the protein level as well. To characterise the electrophysiological difference between OA and healthy chondroprogenitor cells, the researchers developed a new method, 3D dielectrophoresis, which provides information on membrane and cytoplasm conductivity at population level. Results showed differences in cellular response and resting membrane potential following administration of an inhibitor and activator identified in an ion channel. Primary research articles on ion channel protein expression and the membranome are expected to be published. The main outcome of CHONDRION is the identification of new plasma membrane biomarkers for the early detection and monitoring of inflammatory changes in OA. Development of new methodologies for characterisation of changes in the diseased chondrocyte can be used in future research.

Keywords

Osteoarthritis, chondrocyte, ion channel, membranome, CHONDRION, biomarker

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