ABSTRACT
Periprosthetic osteolysis induced by orthopedic implant-wear particles continues to be the leading cause of arthroplasty failure in majority of patients. Release of the wear debris results in a chronic local inflammatory response typified by the recruitment of immune cells, including macrophages. The cellular mediators derived from activated macrophages favor the osteoclast-bone resorbing activity resulting in bone loss at the site of implant and loosening of the prosthetic components. Emerging evidence suggests that chemokines and their receptors are involved in the progression of periprosthetic osteolysis associated with aseptic implant loosening. In the current study, we investigated the potential role of chemokine C-motif-ligand-1 (XCL1) in the pathogenesis of inflammatory osteolysis induced by wear particles. Expressions of XCL1 and its receptor XCR1 were evident in synovial fluids and tissues surrounding hip-implants of patients undergoing revision total hip arthroplasty. Furthermore, murine calvarial osteolysis model induced by ultra-high molecular weight polyethylene (UHMWPE) particles was used to study the role of XCL1 in the development of inflammatory osteolysis. Mice received single injection of recombinant XCL1 onto the calvariae after implantation of particles exhibited significantly greater osteolytic lesions than the control mice. In contrast, blockade of XCL1 by neutralizing antibody significantly reduced bone erosion and the number of bone-resorbing mature osteoclasts induced by UHMWPE particles. In consistence with the results, transplantation of XCL1-soaked sponge onto calvariae caused osteolytic lesions coincident with excessive infiltration of inflammatory cells and osteoclasts. These results suggested that XCL1 might be involved in the development of periprosthetic osteolysis through promoting infiltration of inflammatory cells and bone resorbing-osteoclasts. Our further results demonstrated that supplementing recombinant XCL1 to cultured human monocytes stimulated with the receptor activator of nuclear factor kappa-B ligand (RANKL) promoted osteoclastogenesis and the osteoclast-bone resorbing activity. Moreover, recombinant XCL1 promoted the expression of inflammatory and osteoclastogenic factors, including IL-6, IL-8, and RANKL in human differentiated osteoblasts. Together, these results suggested the potential role of XCL1 in the pathogenesis of periprosthetic osteolysis and aseptic loosening. Our data broaden knowledge of the pathogenesis of aseptic prosthesis loosening and highlight a novel molecular target for therapeutic intervention.
Subject(s)
Antibodies, Neutralizing/pharmacology , Chemokines, C/antagonists & inhibitors , Joints/drug effects , Osteoclasts/drug effects , Osteogenesis/drug effects , Osteolysis/prevention & control , Polyethylenes , Synoviocytes/drug effects , Animals , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/instrumentation , Bone Resorption , Chemokines, C/metabolism , Disease Models, Animal , Female , Hip Prosthesis/adverse effects , Humans , Inflammation Mediators/metabolism , Joints/metabolism , Joints/pathology , Male , Mice, Inbred C57BL , Middle Aged , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoblasts/pathology , Osteoclasts/metabolism , Osteoclasts/pathology , Osteolysis/chemically induced , Osteolysis/metabolism , Osteolysis/pathology , Receptors, G-Protein-Coupled/metabolism , Severity of Illness Index , Signal Transduction , Synoviocytes/metabolism , Synoviocytes/pathologyABSTRACT
Recent in vitro findings suggest that UHMWPE wear particles containing vitamin E (VE) may have reduced biologic activity and decreased osteolytic potential. We hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE would cause less osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Groups received equal amount of particulate debris overlaying the calvarium for 10 days. Calvarial bone was examined using high resolution micro-CT and histomorphometric analyses. There was a statistically significant difference between virgin (12.2%±8%) and VE-UHMWPE (3%±1.4%) groups in regards to bone resorption (P=0.005) and inflammatory fibrous tissue overlaying the calvaria (0.48 vs. 0.20, P<0.0001). These results suggest that VE-UHMWPE particles have reduced osteolytic potential in vivo when compared to virgin UHMWPE.
Subject(s)
Osteolysis/etiology , Osteolysis/prevention & control , Polyethylenes/pharmacology , Skull/pathology , Vitamin E/pharmacology , Animals , Disease Models, Animal , Gamma Rays , Male , Mice, Inbred C57BL , Microscopy, Electron, Scanning , Particle Size , Random Allocation , Skull/diagnostic imaging , X-Ray MicrotomographyABSTRACT
After total hip arthroplasty, long-term complications such as loosening, wear, osteolytic lesion and granulomatous reaction by foreign bodies can occur. Granulomatous reaction is a chronic inflammatory reaction caused by polyethylene debris, which is rarely present as a mass. The case of a pseudotumor, which required surgical intervention because of pain and its large size with compression symptoms, has not been reported yet. This 70 year old male patient was admitted complaining of RLQ pain, a palpable mass and compressed adjacent organs, 2 years after a revision total hip arthroplasty performed in September 1999. During the operation, a well-encapsulated large mass was noted, which was near the lateral side of the iliopsoas muscle and compressed the femoral nerve from the posterolateral side. Here, we report a case of pseudotumor caused by polyethylene wear debris.