Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues

Abstract

Mechanotransduction is a fundamental ability that allows living organisms to receive and respond to physical signals from both the external and internal environments. The mechanotransduction process requires a range of special proteins termed mechanotransducers to convert mechanical forces into biochemical signals in cells. The Piezo proteins are mechanically activated nonselective cation channels and the largest plasma membrane ion channels reported thus far. The regulation of two family members, Piezo1 and Piezo2, has been reported to have essential functions in mechanosensation and transduction in different organs and tissues. Recently, the predominant contributions of the Piezo family were reported to occur in the skeletal system, especially in bone development and mechano-stimulated bone homeostasis. Here we review current studies focused on the tissue-specific functions of Piezo1 and Piezo2 in various backgrounds with special highlights on their importance in regulating skeletal cell mechanotransduction. In this review, we emphasize the diverse functions of Piezo1 and Piezo2 and related signaling pathways in osteoblast lineage cells and chondrocytes. We also summarize our current understanding of Piezo channel structures and the key findings about PIEZO gene mutations in human diseases.

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

“…Based on our findings of this study that Kindlin-2 expression is dramatically reduced in condylar chondrocytes of aged TMJ and that Kindlin-2 loss causes osteoarthritic lesions in mouse TMJ that highly mimic those in human TMJ OA, along with the fact that abnormal and sustained mechanical stress plays a critical role in pathogenesis of TMJ and knee joint OAs and established role of the focal adhesion pathway in mediation of mechanotransduction in skeleton, 8 , 29 , 44 – 46 it will be crucial to investigate if changes in Kindlin-2 expression, especially in condylar chondrocytes, play a role in the pathogenesis of TMJ OA in humans.…”

Iron Oxide Nanoparticles Combined with Static Magnetic Fields in Bone Remodeling

“…Piezo-type mechanosensitive ion channel component 1 (Piezo1), a recently identified bona fide mechanotransducer, confers mechanosensitivity on osteoblasts and plays a critical role in bone formation [ 103 ]. To date, the only method known to activate Piezo1 is mechanical stimulation, except for the chemical agonist Yoda1 [ 104 ].…”

Osteocyte β1 integrin loss causes low bone mass and impairs bone mechanotransduction in mice

“…With the advances of technologies for the past twenty to thirty years, recent studies demonstrate that osteocyte is an emerging multi-functional orchestrator in bone remodeling [ 23 ] through direct regulation of local calcium abundance and phosphate metabolism [ 24 , 25 ], indirect modulation of osteoblast and osteoclast activities [ 25 , 26 ]. Importantly, osteocytes have been demonstrated as the principal mechano-responsive cells in bone [ 19 , 21 , [27] , [28] , [29] ].…”