Abstract 42

Apoptosis and Peri-implant Osteolysis: Expression of Trail and its receptors in revision tissue adjacent to osteolytic lesions

Holding CA¹, McGrath R¹, Dharmapatni K¹, Stamenkov R², Neale SD², Findlay DM², Atkins GJ ² and Haynes DR¹

¹Department of Pathology, Adelaide University, South Australia, 5005, Australia.
²Department of Orthopaedics and Trauma, Adelaide University, South Australia, 5000, Australia.

The unregulated bone resorption that occurs in osteolytic regions surrounding failed joint implants is associated with an increased number of active osteoclasts that persist within the invading soft tissue. It has been proposed that these osteoclasts may prevail in situ due to an altered expression of a normal apoptotic signalling apparatus. The aim of this study was to investigate the expression of the apoptotic factor TRAIL and its four membrane bound receptors in tissues obtained from sites of peri-implant osteolysis in patients undergoing revision surgery for failed hip prosthesis. Immunohistochemical analysis of formalin fixed sections from 10 patients undergoing revision surgery was performed using monoclonal antibodies directed against TRAIL, and the TRAIL receptors R1, R2, R3 and R4. Control tissue consisted of synovial tissue samples taken from patients with osteoarthritis undergoing primary hip replacement surgery. Sections were evaluated by light microscopy using a scoring system that has been used in several of our publications. Elevated levels (p<0.005) of staining for TRAIL, TRAIL-R1, TRAIL-R3 and TRAIL-R4 was found in tissues from failed prosthesis, with staining associated with both multinucleated osteoclast-like cells and mononuclear inflammatory cells. The increased expression of both decoy receptors TRAIL-R3 and R4 may contribute to the perpetuation of the osteoclasts within the sites of osteolysis, despite the increased presence of TRAIL and death receptors capable of transmitting the apoptotic signal. Targeted intervention of the TRAIL decoy receptors may represent a potential therapeutic target in diseases where there is unwanted bone destruction by osteoclasts.

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