title: Differential gene expression in the periprosthetic membrane: lubricin as a new possible pathogenetic factor in prosthesis loosening.
abstract: About 10% of hip endoprostheses will loosen after 10 years. Prosthesis loosening is caused by two different pathomechanisms: aseptic loosening (AL) and septic loosening (SL). This study evaluated differences in gene expression in AL and SL. Eight hybridizations were performed on PIQOR cDNA arrays. Objects of the study were periprosthetic interface tissue samples from two patients with SL and three patients with AL. Tissue parts directly adjacent to the site of RNA isolation were analyzed immuno/histopathologically in order to overcome the problem of tissue heterogeneity. Thirty-three genes were found constantly differentially expressed, among which were cd11b, cd18, cd68, osteopontin and ferritin heavy-chain upregulated in AL and collagen types 1alpha-1, 3alpha-1, integrin alpha-1, thrombospondin2 and nidogen upregulated in SL. The most striking finding was the strong upregulation (from 20-fold to 323-fold) of megakaryocyte stimulating factor (msf) in all aseptic cases and one of the two septic cases, which was confirmed by real-time reverse transcription-polymerase chain reaction. In this study, msf is linked to prosthesis loosening for the first time. The upregulation in AL suggests an important pathogenetic role: the msf splice product lubricin is responsible for the lubrication of healthy joints, but its excellent lubrication ability may disturb the tight interaction between bone and prosthesis and thereby contribute to prosthesis loosening.
authors.affiliation: Institute for Pathology, University Clinic Charité, Charité University Hospital, Humboldt University of Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Morawietz
authors.forename: Thorsten
authors.initials: T
authors.lastname: Gehrke
authors.forename: Lars
authors.initials: L
authors.lastname: Frommelt
authors.forename: Petra
authors.initials: P
authors.lastname: Gratze
authors.forename: Andreas
authors.initials: A
authors.lastname: Bosio
authors.forename: Johannes
authors.initials: J
authors.lastname: Möller
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gerstmayer
authors.forename: Veit
authors.initials: V
authors.lastname: Krenn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019645:Arthroplasty, Replacement, Knee; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007720:Knee Prosthesis; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011475:Prosthesis Failure; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011509:Proteoglycans; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D000099158:Proteoglycan 4
chemical_list: D006023:Glycoproteins; D011506:Proteins; D011509:Proteoglycans; D012313:RNA; D000099158:Proteoglycan 4; C419197:PRG4 protein, human