title: Characteristic Markers of the WNT Signaling Pathways Are Differentially Expressed in Osteoarthritic Cartilage.
abstract: OBJECTIVE
  It is well known that expression of markers for WNT signaling is dysregulated in osteoarthritic (OA) bone. However, it is still not fully known if the expression of these markers also is affected in OA cartilage. The aim of this study was therefore to examine this issue.
  
  
  METHODS
  Human cartilage biopsies from OA and control donors were subjected to genome-wide oligonucleotide microarrays. Genes involved in WNT signaling were selected using the BioRetis database, KEGG pathway analysis was searched using DAVID software tools, and cluster analysis was performed using Genesis software. Results from the microarray analysis were verified using quantitative real-time PCR and immunohistochemistry. In order to study the impact of cytokines for the dysregulated WNT signaling, OA and control chondrocytes were stimulated with interleukin-1 and analyzed with real-time PCR for their expression of WNT-related genes.
  
  
  RESULTS
  Several WNT markers displayed a significantly altered expression in OA compared to normal cartilage. Interestingly, inhibitors of the canonical and planar cell polarity WNT signaling pathways displayed significantly increased expression in OA cartilage, while the Ca(2+)/WNT signaling pathway was activated. Both real-time PCR and immunohistochemistry verified the microarray results. Real-time PCR analysis demonstrated that interleukin-1 upregulated expression of important WNT markers.
  
  
  CONCLUSIONS
  WNT signaling is significantly affected in OA cartilage. The result suggests that both the canonical and planar cell polarity WNT signaling pathways were partly inhibited while the Ca(2+)/WNT pathway was activated in OA cartilage.
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Laboratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Thorfve
authors.affiliation: Department of Rheumatology and Clinical Immunology, Tissue Engineering Laboratory and Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Dehne
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Laboratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Lindahl
authors.affiliation: Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Brittberg
authors.affiliation: Institute of Transfusion Medicine, Tissue Bank, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Pruss
authors.affiliation: Department of Rheumatology and Clinical Immunology, Tissue Engineering Laboratory and Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Ringe
authors.affiliation: Department of Rheumatology and Clinical Immunology, Tissue Engineering Laboratory and Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sittinger
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Laboratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Karlsson
keywords: articular cartilage < tissue; biopsy < research methods; osteoarthritis < diagnosis; signaling molecules < cytokines and growth factors