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2012 ; 3
(1
): 43-57
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Characteristic Markers of the WNT Signaling Pathways Are Differentially Expressed
in Osteoarthritic Cartilage
#MMPMID26069618
Thorfve A
; Dehne T
; Lindahl A
; Brittberg M
; Pruss A
; Ringe J
; Sittinger M
; Karlsson C
Cartilage
2012[Jan]; 3
(1
): 43-57
PMID26069618
show ga
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.