Therapeutic Potential of Chemical Chaperone 4-phenylbutyrate in Modulating Wear Particle-Induced Macrophage-Mediated Inflammatory Injury

The effects of 4-phenylbutyrate (4-PBA) on particle-induced macrophage apoptosis in vitro have not been previously documented. This study aims to investigate the thera-peutic potential of 4-PBA in alleviating titanium nanoparticle (TiNP)-induced in-flammatory injury mediated by macrophages. Our findings demonstrate that TiNPs exhibit specific properties capable of inciting inflammatory injury to macrophages. Furthermore, the extent of inflammatory injury inflicted by TiNPs on macrophages progressively increases in correlation with both the concentration of particles and du-ration of exposure. Exposure to TiNPs significantly reduces macrophage viability, promotes apoptosis, enhances the expression of inflammatory cytokines, and exacer-bates the production of reactive oxygen species (ROS). Co-treatment with 4-PBA sig-nificantly alleviates the severity of particle-induced inflammatory injury while simul-taneously facilitating apoptosis in stressed macrophages. Pharmacological intervention with 4-PBA facilitates TiNP-induced macrophage apoptosis by increasing the expres-sion of pro-apoptotic proteins such as Caspase-3 and Bax, while decreasing the levels of anti-apoptotic protein Bcl-2. When used as an independent treatment, 4-PBA does not provoke a pronounced inflammatory response nor induce significant changes in mac-rophage apoptosis, underscoring its potential as a safe therapeutic option. These find-ings substantiate the hypothesis that employing a specific approach to facilitate mac-rophage apoptosis could serve as an effective therapeutic strategy for managing aseptic loosening. Significantly, this approach demonstrates a favorable safety profile, posi-tioning it as a promising avenue for future clinical applications in this domain.