Potential Role of the PGE2-EP4-Ca2+ Signaling Axis in Post-Traumatic Osteoarthritis

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease triggered by trauma or intense mechanical stress, leading to joint cartilage degeneration and functional impairment. Prostaglandin E2 (PGE2) contributes significantly to cartilage degradation following mechanical injury by activating its receptor, Prostaglandin E receptor 4 (EP4), on chondrocyte membranes. The homeostasis of articular cartilage primarily relies on the dynamic balance between cartilage degradation and repair, a process finely regulated by chondrocytes. The Ca²⁺/Calmodulin-dependent Protein Kinase II (CAMKII) signaling pathway has been shown to play a critical role in mediating chondrocyte function restoration. In this study, we observed increased expression of EP4, Inositol 1,4,5-trisphosphate receptor (IP3R), and phosphorylated CaMKII in interleukin-1 beta (IL-1β) stimulated chondrocytes, suggesting a possible link between EP4 signaling and calcium dysregulation. However, direct evidence confirming the involvement of the EP4-Ca²⁺/CaMKII axis in PTOA is still lacking. Further investigations using genetic or pharmacological interventions are needed to clarify this potential mechanism. These findings provide a preliminary basis for exploring calcium homeostasis and EP4 signaling as targets for PTOA treatment.