The potential role of mechanically sensitive ion channels in the physiology, injury, and repair of articular cartilage

Abstract

Biomechanical factors play an extremely important role in regulating the function of articular chondrocytes. Understanding the mechanical factors that drive chondrocyte biological responses is at the heart of our interpretation of cascade events leading to changes in articular cartilage osteoarthritis. The mechanism by which mechanical load is transduced into intracellular signals that can regulate chondrocyte gene expression remains largely unknown. The mechanically sensitive ion channel (MSC) may be one of its specific mechanisms. This review focuses on four ion channels involved in the mechanotransduction of chondrocytes, exploring their properties and the main factors that activate the associated pathways. The upstream and downstream potential relationships between the protein pathways were also explored. The specific biophysical mechanism of the chondrocyte mechanical microenvironment is becoming the focus of research. Elucidating the mechanotransduction mechanism of MSC is essential for the research of biophysical pathogenesis and targeted drugs in cartilage injury-related diseases.

Computational and experimental studies of a cell-imprinted-based integrated microfluidic device for biomedical applications

“…To preserve a sufficient amount of cartilage, mechanotransduction in chondrocytes enables them to change the composition of www.nature.com/scientificreports/ the extracellular matrix (ECM). The cartilage can be damaged if mechanotransduction pathways are disturbed, leading to osteoarthritis and other joint diseases 73,74 . TRPV4 is abundantly expressed in articular chondrocytes, and loss of TRPV4 activity leads to osteoarthritis and joint arthropathy.…”

“…Excessive activation of the Piezo1 ion channel, which can sense mechanical stimulus too, can cause apoptosis and mechanical injury. When a high-strain mechanical load is transferred to chondrocytes, which may cause injury, Piezo1 channel protein is activated, whereas low-strain physiologic loading is mediated by TRPV4 [73][74][75][76][77][78] . One of the earliest responses of chondrocytes to physical stimulus is [Ca 2+ ] i signaling.…”

Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone

“…By sensing and responding to mechanical stimuli, bone cells adapt to the mechanical environment and maintain bone homeostasis [ 6 , 9 , 10 ]. Moreover, chondrocytes, the primary cell type of cartilage that is also involved in bone development, are also stimulated by mechanical stimuli [ 11 ]. Therefore, cellular mechanotransduction is crucial for bone development and physiology, and abnormal cellular mechanotransduction leads to various bone diseases, including osteoporosis (OP) and osteoarthritis (OA) [ 12 , 13 ].…”

Mechanosensory and mechanotransductive processes mediated by ion channels in articular chondrocytes: Potential therapeutic targets for osteoarthritis

“…Mechanical forces stimulate the synthesis and release of matrix proteins and glycosaminoglycan in articular cartilage via complex molecular mechanisms, including mechanical regulation of ion channels such as K + channels, Ca 2+ channels and Na + /K + pumps and stretch-activated channels (SACs). The common denominator of this channel activity is often mechanical activation of the Ca 2+ signaling pathways [19][20][21][22][23][24][25][26][27]. A lack of mechanosensitive ion channels, such as ENaC and transient receptor potential vanilloid 4 (TRPV4) has been shown to impair the mechanical sensitivity of chondrocytes in response to mechanical membrane strain induced by hypotonic solution [23,[28][29][30].…”