IRE1-mediated ER Stress Pathway Of Cell Apoptosis May Participate In Particle-induced Aseptic Loosening Of Knee Arthroplasty In Rabbits

Objective To designed a novel aseptic loosening model of knee periarthroplasty in rabbits and explored whether IRE1-mediated ER stress pathway of cell apoptosis may participate in particle-induced aseptic loosening of knee arthroplasty in rabbits.Methods In the36rabbit knee arthroplasty models(average and random into PMMA-KA group,KA group,shame operated group),we drilled a hole in left intercondylar fossa femur and screwed into a prosthesis which is a part of biological mortar cup from LINK CO.Germany.The PMMA-KA(n=12) group injected into lug PMMA particles before scewing into the prosthesis.After12weeks, to confirme aseptic loosening of the PMMA-KA group,we took out radiographs analysis and HE staining of the femoral samples, detected StrACP activity and TNF-a concentration in the interface membrane and capsuls aroud the prosthesis.The interface membrane and capsuls aroud the prosthesis were detected for apoptotic cells by TUNEL method.Furthermore,Western blot was performed to evaluate the levels of IRE1、TRAF2、ASK1and JNK in these soft tissues. These markers were regarded as apoptotic inducers or specific indicators of ER stress pathway of apoptosis.Results Radiographs analysis and HE staining of the femoral samples as well as detection of StrACP activity and TNF-α concentration of the interface membrane and capsuls aroud the prosthesis confirmed aseptic loosening of the PMMA-KA group.The results of TUNEL staining demonstrated that there were more apoptotic cells in the PMMA-KA group(P<0.05).The expression levels of IRE1、TRAF2、ASK1and JNK were significantly increased in the PMMA-KA group than the other groups(P<0.05).Conclusion Our reselts suggest that IRE1-mediated ER stress pathway may participate in cell apoptosis in particle-induced aseptic loosening of knee arthroplasty in rabbits. A therapeutic target to modulate the ER stress apoptotic pathway may be a strategy to prevent and treat aseptic loosening.Besides,this joint loose model worth being improved and popularized.