Original Article

Virchows Archiv

, Volume 443, Issue 1, pp 57-66

First online:

Differential gene expression in the periprosthetic membrane: lubricin as a new possible pathogenetic factor in prosthesis loosening

  • Lars MorawietzAffiliated withInstitute for Pathology, University Clinic Charité, Charité University Hospital, Humboldt University of Berlin
  • , Thorsten GehrkeAffiliated withENDO-Klinik Hamburg
  • , Lars FrommeltAffiliated withENDO-Klinik Hamburg
  • , Petra GratzeAffiliated withInstitute for Pathology, University Clinic Charité, Charité University Hospital, Humboldt University of Berlin
  • , Andreas BosioAffiliated withMemorec Stoffel GMBH
  • , Johannes MöllerAffiliated withInstitute for Pathology, University Clinic Charité, Charité University Hospital, Humboldt University of Berlin
  • , Bernhard GerstmayerAffiliated withMemorec Stoffel GMBH
  • , Veit KrennAffiliated withInstitute for Pathology, University Clinic Charité, Charité University Hospital, Humboldt University of Berlin Email author 

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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.

Keywords

Aseptic prosthesis loosening Septic prosthesis loosening cDNA array msf Lubricin