Mechanoelectrical transduction in chondrocytes

Abstract

Cartilage tissue lines the joints of mammals, helping to lubricate joint movement and distribute mechanical loads. This tissue is comprised of isolated cells known as chondrocytes which are embedded in an extracellular matrix. Chondrocytes produce and maintain the cartilage by sensing and responding to changing mechanical loads. Mechanosensitive ion channels have been implicated in chondrocyte mechanotransduction and recent studies have shown that both PIEZO1 and TRPV4 can be activated by mechanical stimuli in these cells. The 2 channels mediate separate but overlapping mechanoelectrical transduction pathways, PIEZO1 in response to stretch and substrate deflections and TRPV4 in response to substrate deflections alone. These distinct pathways of mechanoelectrical transduction suggest a mechanism by which chondrocytes can distinguish between different stimuli that arise in their complex mechanical environment.

Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation

“…One is the non-selective depolarizing stretch-activated ion channel (SAC), which allows the influx of cations such as Ca 2+ , Na + , and K + into the cell in response to mechanical or hypo-osmotic stress. SACs include the epithelial sodium channel (ENaC) family [33] , the transient receptor potential (TRP) channel family [33] , [34] , [35] , and the Piezo1 and Piezo2 channels [36] . The other one is the selective hyperpolarizing potassium channel, which includes the voltage-gated potassium channel (VGCs K ) and stretch-activated potassium channel (SACs K ).…”

Analysis of Mechanically Activated Ion Channels at the Cell-Substrate Interface: Combining Pillar Arrays and Whole-Cell Patch-Clamp

“…The channel activity in cells cultured on the arrays is monitored using whole-cell patch-clamp and stimuli are applied by deflecting an individual pilus subjacent to the cell. Pillar deflection has been shown to evoke PIEZO1, PIEZO2 (Poole et al, 2014) and TRPV4 (Servin-Vences et al, 2017; Tay et al, 2018) mediated currents and to evoke MA channel activity in primary cells, such as somatosensory neurons and chondrocytes (Poole et al, 2014; Servin-Vences et al, 2017, 2018; Wetzel et al, 2017). The technique is quantitative and preserves transmembrane force-sensing structures incorporating the substrate, extracellular matrix (ECM), cell attachments and intracellular components, such as STOML3, that can tune the sensitivity of the MA channels (Poole et al, 2014; Wetzel et al, 2017).…”

Collagen Organization Within the Cartilage of Trpv4−/− Mice Studied with Two‐Photon Microscopy and Polarized Second Harmonic Generation

“…In contrast, in cells isolated from a Trpv4 −/− mouse, mechanosensitive channel activity was only reduced to around 50%, indicating a compensatory current was present when TRPV4 was chronically ablated. Knockdown of PIEZO1 transcripts in the Trpv4 −/− cells completely ablated the currents, suggesting that PIEZO1 can compensate for a chronic loss of TRPV4 . In addition, the cartilage is a complex environment where collagen II fibers associate with proteoglycans and other collagens to stabilize the network .…”