Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms24097868
Keywords
mechanotransduction; human chondrocytes; Piezo1; TRPV4; calcium signaling
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Osteoarthritis is a common degenerative joint disease that causes pain and functional limitations. Physical activity is an effective intervention in alleviating pain and promoting joint function. Dysfunction of mechanosensitive ion channels in chondrocytes plays a crucial role in the progression of OA.
Osteoarthritis (OA) is the most common degenerative joint disease causing pain and functional limitations. Physical activity as a clinically relevant, effective intervention alleviates pain and promotes joint function. In chondrocytes, perception and transmission of mechanical signals are controlled by mechanosensitive ion channels, whose dysfunction in OA chondrocytes is leading to disease progression. Signaling of mechanosensitive ion channels Piezo/TRPV4 was analyzed by Yoda1/GSK1016790A application and calcium-imaging of Fura-2-loaded chondrocytes. Expression analysis was determined by qPCR and immunofluorescence in healthy vs. OA chondrocytes. Chondrocytes were mechanically stimulated using the Flexcell (TM) technique. Yoda1 and GSK1016790A caused an increase in intracellular calcium [Ca2+](i) for Yoda1, depending on extracellularly available Ca2+. When used concomitantly, the agonist applied first inhibited the effect of subsequent agonist application, indicating mutual interference between Piezo/TRPV4. Yoda1 increased the expression of metalloproteinases, bone-morphogenic protein, and interleukins in healthy and OA chondrocytes to a different extent. Flexcell (TM)-induced changes in the expression of MMPs and ILs differed from changes induced by Yoda1. We conclude that Piezo1/TRPV4 communicate with each other, an interference that may be impaired in OA chondrocytes. It is important to consider that mechanical stimulation may have different effects on OA depending on its intensity.
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