NDLI: Tight regulation of wingless-type signaling in the articular cartilage - subchondral bone biomechanical unit: transcriptomics in Frzb-knockout mice

Content Provider	Springer Nature : BioMed Central
Author	Lodewyckx, Liesbet Cailotto, Frédéric Thysen, Sarah Luyten, Frank P Lories, Rik J
Abstract	Introduction The aim of this research was to study molecular changes in the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled-related protein (Frzb) compared to wild-type mice by transcriptome analysis. Methods Gene-expression analysis of the articular cartilage and subchondral bone of three wild-type and three Frzb -/- mice was performed by microarray. Data from three wild-type and two Frzb -/- samples could be used for pathway analysis of differentially expressed genes and were explored with PANTHER, DAVID and GSEA bioinformatics tools. Activation of the wingless-type (WNT) pathway was analysed using Western blot. The effects of Frzb gain and loss of function on chondrogenesis and cell proliferation was examined using ATDC5 micro-masses and mouse ribcage chondrocytes. Results Extracellular matrix-associated integrin and cadherin pathways, as well as WNT pathway genes were up-regulated in Frzb -/- samples. Several WNT receptors, target genes and other antagonists were up-regulated, but no difference in active β-catenin was found. Analysis of ATDC5 cell micro-masses overexpressing FRZB indicated an up-regulation of aggrecan and Col2a1, and down-regulation of molecules related to damage and repair in cartilage, Col3a1 and Col5a1. Silencing of Frzb resulted in down-regulation of aggrecan and Col2a1. Pathways associated with cell cycle were down-regulated in this transcriptome analysis. Ribcage chondrocytes derived from Frzb -/- mice showed decreased proliferation compared to wild-type cells. Conclusions Our analysis provides evidence for tight regulation of WNT signalling, shifts in extracellular matrix components and effects on cell proliferation and differentiation in the articular cartilage - subchondral bone unit in Frzb -/- mice. These data further support an important role for FRZB in joint homeostasis and highlight the complex biology of WNT signaling in the joint.
Related Links	https://arthritis-research.biomedcentral.com/counter/pdf/10.1186/ar3695.pdf
Ending Page	18
Page Count	18
Starting Page	1
File Format	HTM / HTML
ISSN	14786362
DOI	10.1186/ar3695
Journal	Arthritis Research & Therapy
Issue Number	1
Volume Number	14
Language	English
Publisher	BioMed Central
Publisher Date	2012-01-20
Access Restriction	Open
Subject Keyword	Rheumatology Orthopedics Articular Cartilage Subchondral Bone Type Versus Collagen ATDC5 Cell Robust Multiarray Average
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Rheumatology
Journal Impact Factor	4.4/2023
5-Year Journal Impact Factor	4.9/2023

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