RESUMO
Wear particle-induced orthopaedic prosthesis loosening is associated with elevated osteoclast activity. The immunoreceptor tyrosine-based activation motif (ITAM)-related molecules OSCAR, FcRγ, TREM2 and DAP12 are important for osteoclast formation. The aim of this study was to determine if these molecules are involved in peri-implant loosening by investigating their expression in peri-implant tissues obtained at revision of joint replacement components containing polyethylene (PE) wear particles, and in osteoclasts formed in vitro in the presence of PE particles. The results showed that there was a marked and statistically significant increase in protein levels of the ITAM-related molecules in the revision tissues. The levels of OSCAR, FcRγ, TREM2 and DAP12 mRNA in the revision tissues were also increased. In vitro PE particles stimulated osteoclast resorption in the presence of 50 ng ml(-1) receptor activator NFκB (RANKL) and significantly elevated the expression of OSCAR, FcRγ, TREM2 and DAP12 during osteoclast formation. These findings suggest that the ITAM signalling molecules and their co-receptors have a role in pathogenic bone loss associated with implant PE wear.
Assuntos
Prótese Articular , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Polietilenos/farmacologia , Próteses e Implantes , Receptores Imunológicos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Dentina/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Osteoartrite/patologia , Osteoclastos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Imunológicos/genética , Doadores de TecidosRESUMO
This study investigates receptor activator NF-kappaB (RANK), RANK ligand (RANKL) and tumour necrosis factor (TNFalpha), key factors regulating bone turnover, present in the tissues near peri-prosthetic osteolysis. Tissue was obtained from zones of peri-prosthetic osteolysis from 11 patients undergoing revision of total hip prostheses, analysed preoperatively by high-resolution spiral multislice CT using a metal artefact suppression protocol. Synovial tissue from 10 patients with osteoarthritis undergoing primary hip replacement was used as control tissue. Immunohistochemical analysis of formalin fixed tissue sections demonstrated that RANK, RANKL and TNFalpha were strongly expressed by large multinucleated cells containing polyethylene wear debris in revision tissues. Control tissue stained weakly for RANK, RANKL and TNFalpha. A strong statistical correlation (p<0.02) was found between the five parameters, volume of bone loss, polyethylene wear debris, RANK, RANKL and TNFalpha expression. Importantly, in vitro studies revealed that RANKL and TNFalpha synergise to increase the volume of bone resorbed, by more than seven fold, when compared to the effect of either cytokine treatment alone. This suggests that the interaction of TNFalpha and RANKL promotes osteoclast activity associated with polyethylene wear and therapies targeting TNF activity may be useful to treat peri-implant osteolysis.
