Expression And Significance Of RANKL, MMP-9 And TIMP-1 In Periprosthetic Tissues Of Aseptic Loosened Total Hip Prosthesis

Objective: To detect and compare the expressions and localization of RANKL, MMP-9 and TIMP-1 in aseptic periprosthetic interface membranes, hip osteoarthritis and normal hip joint synovial tissues. To explore the role and relationship of RANKL, MMP-9 and TIMP-1 in the development of aseptic loosening of the prosthesis after total hip arthroplasty. To investigate whether the pathogenesis of aseptic loosening and osteoarthritis are identical or not.Methods: The samples were divided into three groups: 47 cases of aseptic loosening of hip prosthesis interface membrane around the tissue samples(aseptic loosening group, including 27 cases of bone cement prosthesis and 20 cases of biological prosthesis interface membrane around the organization samples), 20 cases of hip osteoarthritis synovial tissue specimens(osteoarthritis group) and 20 cases of femoral neck fracture of hip joint synovial tissue specimens(femoral neck fracture group). All specimens were subjected to detect the expressions of RANKL, MMP-9 and TIMP-1 by SABC immunohistochemical method. Then immunohistochemical results were illustrated by the average integral optical density(IOD) of stainings which were analyzed by Image pro-Plus 6.0 software. Then, the results were statistically analyzed by SPSS18.0 software.Results: 1. RANKL, MMP-9 and TIMP-1 mainly expressed in cytoplasm and membrane of macrophages in aseptic loosening group and osteoarthritis group. And the IOD of RANKL, MMP-9 and TIMP-1 in in aseptic loosening group and osteoarthritis group was larger than that of in femoral neck fracture group(P <0.05). In addition, the ratio of MMP-9 than TIMP-1 were imbalance, and the expression of MMP-9 was correlated positively with that of RANKL in aseptic interface membrane(r=0.871,P =0.002<0.05).2. The expression of RANKL, MMP-9 and TIMP-1 in the bone cement prosthesis and biological prosthesis interface membrane around the organization was no significant difference(P >0.05).3. The IOD of RANKL, MMP-9 and TIMP-1 in hip osteoarthritis synovial tissue were higher than that of in femoral neck fracture group(P <0.05), and There was no significant difference in expression of RANKL, MMP-9 and TIMP-1 in between aseptic loosening group and osteoarthritis group(P >0.05). Similarly, the ratio of MMP-9 than TIMP-1 were also imbalance, and the expression of MMP-9 was correlated positively with that of RANKL in hip osteoarthritis synovial tissues(r=0.820,P =0.006<0.05).Conclusion: 1. RANKL, MMP-9 and TIMP-1 were overexpressed in aseptic loosening periprosthetic interface membranes. RANKL can upregulate the expression of MMP-9 and lead to the imbalance ratio of MMP-9 than TIMP-1, which may account for the mechanisms of aseptic loosening prosthesis.2. The RANKL, MMP-9 and TIMP-1 expressions were similar in the different type of prosthesis(bone cement type or biological type).3. Aseptic loosening and osteoarthritis may have similarities in the pathogenesis of the disease.