title: Polyethylene particles stimulate expression of ITAM-related molecules in peri-implant tissues and when stimulating osteoclastogenesis in vitro.
abstract: 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.
authors.affiliation: Discipline of Anatomy and Pathology, The University of Adelaide, North Terrace, Adelaide, South Australia 5005, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Alias
authors.forename: A S S K
authors.initials: AS
authors.lastname: Dharmapatni
authors.forename: A C
authors.initials: AC
authors.lastname: Holding
authors.forename: G J
authors.initials: GJ
authors.lastname: Atkins
authors.forename: D M
authors.initials: DM
authors.lastname: Findlay
authors.forename: D W
authors.initials: DW
authors.lastname: Howie
authors.forename: T N
authors.initials: TN
authors.lastname: Crotti
authors.forename: D R
authors.initials: DR
authors.lastname: Haynes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003804:Dentin / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007595:Joint Prosthesis; D008297:Male; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000473:pathology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D011095:Polyethylenes / Q000494:pharmacology*; D019736:Prostheses and Implants; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D014019:Tissue Donors
chemical_list: D050778:NFATC Transcription Factors; D011095:Polyethylenes; D012333:RNA, Messenger; D011971:Receptors, Immunologic