Abstract
BACKGROUND: Aseptic loosening commonly leads to surgical failure and revision arthroplasty after total hip arthroplasty (THA). C-X-C motif chemokine ligand 16 (CXCL16), a chemokine involved in various inflammatory and immune responses, has been implicated in bone metabolism. This single-institution study investigated the association between CXCL16 and aseptic loosening following THA. METHODS: We compared 100 patients who underwent revision THA due to aseptic loosening (experimental group) to 100 patients who underwent primary THA for femoral neck fracture or congenital hip dysplasia (control group). Immunohistochemistry and RT-PCR were used to assess CXCL16 expression at the protein and mRNA levels. Double immunofluorescence staining determined the RANKL/OPG ratio in periarticular synovial tissues. Statistical analysis included a chi-square test for CXCL16 protein expression differences and Pearson correlation for the relationship between CXCL16 mRNA expression and RANKL/OPG. RESULTS: Proteomics analysis revealed significantly higher CXCL16 expression in the experimental group compared to the control group (p < .01). Immunohistochemistry confirmed that 90% of samples in the experimental group showed positive CXCL16 staining compared to 7% in the control group (p < .01). RT-PCR demonstrated a 3.4-fold higher CXCL16 mRNA expression in the experimental group relative to controls (p < .01). TRAP staining identified that 72% of CXCL16+ multinucleated giant cells in the experimental group were macrophages. Immunohistochemical staining showed that 73% of CXCL16+ macrophages were M2 type, and 27% were M1 type. Dual-immunofluorescence staining indicated an increase in the RANKL/OPG ratio in the experimental group, with a positive linear correlation between CXCL16 mRNA expression and the RANKL/OPG ratio (r = .919, p < .01). CONCLUSION: Our findings reveal a significant association between elevated CXCL16 expression and an increased RANKL/OPG ratio in periprosthetic synovial tissues, suggesting a role for CXCL16 in promoting osteoclast differentiation and activity. These findings offer preliminary insights into CXCL16 as a biomarker and a potential therapeutic target for managing bone resorption in aseptic loosening.