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

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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.

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Acknowledgements

We thank Prof. Reinhold Schäfer and Mrs. Claudia Campisi for their lectorship. The technical assistance of Mrs. Gabriele Fernahl and Mrs. Janine Karle is gratefully acknowledged. The present work was partially supported by the SFB421 and by the Gemeinnütziger Verein ENDO-Klinik e.V., Hamburg (project W1/01, T.G., L.F., M.D., V.K.).

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Authors and Affiliations

  1. Institute for Pathology, University Clinic Charité, Charité University Hospital, Humboldt University of Berlin, Schumannstrasse 20/21, 10117 , Berlin, Germany

    Lars Morawietz, Petra Gratze, Johannes Möller & Veit Krenn

  2. ENDO-Klinik Hamburg, Holstenstrasse 2, 22767 , Hamburg, Germany

    Thorsten Gehrke & Lars Frommelt

  3. Memorec Stoffel GMBH, Cologne, Germany

    Andreas Bosio & Bernhard Gerstmayer

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  1. Lars Morawietz
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Correspondence to Veit Krenn.

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Authors Lars Morawietz and Thorsten Gehrke contributed equally to this work.

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Morawietz, L., Gehrke, T., Frommelt, L. et al. Differential gene expression in the periprosthetic membrane: lubricin as a new possible pathogenetic factor in prosthesis loosening. Virchows Arch 443, 57–66 (2003). https://doi.org/10.1007/s00428-003-0818-y

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  • DOI: https://doi.org/10.1007/s00428-003-0818-y

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