Joint players: Endogenous WNT antagonists determine joint health

Leilei Zhong

Research output: ThesisPhD Thesis - Research UT, graduation UT

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Signaling of the secreted wingless-type MMTV integration site (WNT) has been implicated as a driving factor in osteoarthritis (OA). The induction of chondrocyte hypertrophy is a role attributed to WNT in OA, which may explain why chondrocytes in articular cartilage express high levels of WNT antagonists to modulate the activity of WNT signaling. Dickkopf 1 homolog (DKK1) and frizzled-related protein (FRZB) are naturally occurring antagonists of the WNT signaling pathway. Previously, we identified DKK1 and FRZB as key factors in controlling the articular chondrocyte phenotype by preventing endochondral ossification. The aim of this thesis is to study the role of WNT signaling and its antagonists DKK1 and FRZB in human articular cartilage. In this thesis, we have provided answers for the following questions: i) how does expression of joint-related factors change in cartilage and synovial fluid during OA progression, with a focus on the changes in expression of WNT and WNT antagonists; ii) what is the fundamental role of WNT/β-catenin signaling and its antagonists (DKK1 and FRZB) in human chondrocytes and mesenchymal stem cells; iii) how are WNT antagonists regulated by the inflammatory factor IL1β; and iv) how can we use our knowledge to improve the understanding OA pathology and its treatment.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Twente
  • Karperien, H.B.J., Supervisor
  • Post, J.N., Advisor
Award date31 Aug 2016
Place of PublicationEnschede
Print ISBNs978-94-6233-343-7
Publication statusPublished - 31 Aug 2016


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