Platelet-rich plasma inhibits ferroptosis and inflammation to alleviate frozen shoulder via activating the CST1/GPX4 signaling pathway

Abstract

Platelet-rich plasma (PRP) has been shown to be beneficial to frozen shoulder (FS), but the mechanism of PRP's intervention in FS is still incomplete. Ferroptosis and inflammation are important pathological factors of cartilage injury, but their role in FS has not been explored. In vivo, we found that PRP treatment significantly enhanced the joint range of motion and mitigated joint histopathological damage in FS rats. Notably, levels of iron ions, the ferroptosis marker prostaglandin-endoperoxide synthase 2 (PTGS2), reactive oxygen species (ROS), malondialdehyde (MDA), and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) in the cartilage tissue of PRP-treated rats were significantly reduced. Conversely, levels of superoxide dismutase (SOD) and glutathione (GSH) were markedly increased. In vitro experiments revealed that PRP effectively countered the IL-1β-induced suppression of chondrocyte proliferation while also reducing levels of ferroptosis and inflammation. Furthermore, the CST1/GPX4 pathway was suppressed in the FS environment, while it has the potential to be activated by PRP. Importantly, silencing CST1 negated the therapeutic effects of PRP on IL-1β-treated chondrocytes and FS rats. In summary, we found that PRP alleviated the progression of FS by inhibiting ferroptosis and the inflammatory response by activating the CST1/GPX4 signaling pathway.

Keywords: Ferroptosis; Frozen shoulder; GPX4; Platelet-rich plasma.