Joint players: Endogenous WNT antagonists determine joint health

Leilei Zhong

Research output: ThesisPhD Thesis - Research UT, graduation UT

63 Downloads (Pure)

Abstract

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
Awarding Institution
  • University of Twente
Supervisors/Advisors
  • Karperien, H.B.J., Supervisor
  • Post, J.N., Advisor
Award date31 Aug 2016
Place of PublicationEnschede
Publisher
Print ISBNs978-94-6233-343-7
Publication statusPublished - 31 Aug 2016

Fingerprint

Chondrocytes
Osteoarthritis
Joints
Health
Articular Cartilage
Catenins
Synovial Fluid
Mesenchymal Stromal Cells
Osteogenesis
Hypertrophy
Cartilage
Pathology
Phenotype

Keywords

  • METIS-317466
  • IR-100921

Cite this

Zhong, L. (2016). Joint players: Endogenous WNT antagonists determine joint health. Enschede: Universiteit Twente.
Zhong, Leilei. / Joint players : Endogenous WNT antagonists determine joint health. Enschede : Universiteit Twente, 2016. 218 p.
@phdthesis{5cda007f3af342528d4238f3cc18b46f,
title = "Joint players: Endogenous WNT antagonists determine joint health",
abstract = "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.",
keywords = "METIS-317466, IR-100921",
author = "Leilei Zhong",
year = "2016",
month = "8",
day = "31",
language = "English",
isbn = "978-94-6233-343-7",
publisher = "Universiteit Twente",
school = "University of Twente",

}

Zhong, L 2016, 'Joint players: Endogenous WNT antagonists determine joint health', University of Twente, Enschede.

Joint players : Endogenous WNT antagonists determine joint health. / Zhong, Leilei.

Enschede : Universiteit Twente, 2016. 218 p.

Research output: ThesisPhD Thesis - Research UT, graduation UT

TY - THES

T1 - Joint players

T2 - Endogenous WNT antagonists determine joint health

AU - Zhong, Leilei

PY - 2016/8/31

Y1 - 2016/8/31

N2 - 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.

AB - 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.

KW - METIS-317466

KW - IR-100921

M3 - PhD Thesis - Research UT, graduation UT

SN - 978-94-6233-343-7

PB - Universiteit Twente

CY - Enschede

ER -

Zhong L. Joint players: Endogenous WNT antagonists determine joint health. Enschede: Universiteit Twente, 2016. 218 p.