In summary, advances in understanding the complex role of TRPV4-mediated mechanical signaling mechanisms hold promise for reproducing the physio-biomechanical microenvironment and designing biomaterials with cell-inducing effects for cartilage tissue engineering, and targeting TRPV4-mediated mechanotransduction was proposed as a potential strategy for treating diseases such as osteoarthritis. The gene discussed is TRPV4; the disease is osteoarthritis.