TRPV4 activation induces TMJ degeneration via p38 MAPK/c-Fos/CXCLs axis
Degenerative joint disease mainly manifests abnormal bone and cartilage remodeling, articular disc deformation and synovial inflammation, and it is closely related to intraarticular overload. Activation of the mechanosensitive channel transient receptor potential vanilloid 4 (TRPV4) can lead to degeneration of the temporomandibular joint (TMJ) disc. However, the potential mechanism by which TRPV4 leads to TMJ degeneration are still unclear. The results showed that TRPV4 activation promoted upregulation of chemokines including CXCL6 and CXCL13 in disc cells, and such chemokine release facilitated the proliferation and migration of FLSs and aggravated the TMJ degeneration in rat. Mechanistically, TRPV4-induced p38 MAPK signaling pathway activation promoted chemokine expression via the nuclear translocation of p38 and c-Fos, thereby promoting the proliferation and migration by CXCL-CXCR interaction. Overall design: The primary rat TMJ disc cells were divided into two groups: the control group and the GSK101 group. The disc cells in the GSK101 group were treated with the TRPV4 agonist GSK101 for 24 hours, while those in the control group were treated with DMSO at the same. concentration for 24 hours.