Mechanotransduction is an important process for living cells and tissues by which they experience and respond to mechanical stimuli. Cellular mechanotransduction is crucial for bone development and physiology, and abnormal cellular mechanotransduction leads to various bone diseases, including osteoporosis (OP) and osteoarthritis (OA). Piezo channels are mechanosensitive ion channels located in the cell membrane and function as key cellular mechanotransducers for converting mechanical stimuli into electrochemical signals. The Piezo channels play crucial roles in numerous physiological and pathological process by functioning as cellular mechanotransducers. Under mechanical stimuli, Piezo channels are opened to make cationic ions cross membrane, which promotes cellular mechanotransduction to adapt to the microenvironment.