Activation of the Mechanosensitive Ion Channels Piezo1 and TRPV4 in Primary Human Healthy and Osteoarthritic Chondrocytes Exhibits Ion Channel Crosstalk and Modulates Gene Expression.
Bibiane Steinecker-FrohnwieserBirgit LohbergerStefan ToegelReinhard WindhagerVeronika GlanzCornelia KratschmannAndreas LeithnerLukas WeiglPublished in: International journal of molecular sciences (2023)
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™ technique. Yoda1 and GSK1016790A caused an increase in intracellular calcium [Ca 2+ ] i for Yoda1, depending on extracellularly available Ca 2+ . 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™-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.
Keyphrases
- knee osteoarthritis
- extracellular matrix
- neuropathic pain
- gene expression
- physical activity
- poor prognosis
- randomized controlled trial
- drug delivery
- chronic pain
- rheumatoid arthritis
- high resolution
- binding protein
- spinal cord
- pain management
- body composition
- mass spectrometry
- spinal cord injury
- bone mineral density
- cancer therapy
- small molecule
- postmenopausal women
- fluorescence imaging
- induced pluripotent stem cells