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WNT16 antagonizes excessive canonical WNT activation and protects cartilage in osteoarthritis.

Nalesso, Giovanna, Thomas, BL, Sherwood, JC, Yu, J, Addimanda, O, Eldridge, SE, Thorup, A-S, Dale, L, Schett, G, Zwerina, J, Eltawil, N, Pitzalis, C and Dell’Accio, F (2016) WNT16 antagonizes excessive canonical WNT activation and protects cartilage in osteoarthritis. Annals of the Rheumatic Diseases, 76 (1). pp. 218-226.

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Abstract

Objective. Both excessive and insufficient activation of the WNT signalling result in cartilage breakdown and osteoarthritis. WNT16 is upregulated in the articular cartilage following injury and in osteoarthritis. Here we investigate the function of WNT16 in osteoarthritis and the downstream molecular mechanisms. Methods. Osteoarthritis was induced by destabilisation of the medial meniscus in wild type and WNT16 deficient mice. Molecular mechanisms and downstream effects were studied in vitro and in vivo, in primary cartilage progenitor cells and primary chondrocytes. The pathway downstream of WNT16 was studied in primary chondrocytes and using the axis duplication assay in Xenopus. Results. WNT16 deficient mice developed more severe osteoarthritis with reduced expression of Lubricin and increased chondrocyte apoptosis. WNT16 supported the phenotype of cartilage superficial-zone progenitor cells and Lubricin expression. Increased osteoarthritis in WNT16 deficient mice was associated with excessive activation of canonical WNT signalling. In vitro, high doses of WNT16 weakly activated canonical WNT signalling, but, in co-stimulation experiments, WNT16 reduced the capacity of WNT3A to activate the canonical WNT pathway. In vivo, WNT16 rescued the WNT8-induced primary axis duplication in Xenopus embryos. Conclusion. In osteoarthritis, WNT16 maintains a balanced canonical WNT signalling and prevents detrimental excessive activation thereby supporting the homeostasis of progenitor cells.

Item Type: Article
Subjects : Veterinary Medicine
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
NameEmailORCID
Nalesso, Giovannag.nalesso@surrey.ac.ukUNSPECIFIED
Thomas, BLUNSPECIFIEDUNSPECIFIED
Sherwood, JCUNSPECIFIEDUNSPECIFIED
Yu, JUNSPECIFIEDUNSPECIFIED
Addimanda, OUNSPECIFIEDUNSPECIFIED
Eldridge, SEUNSPECIFIEDUNSPECIFIED
Thorup, A-SUNSPECIFIEDUNSPECIFIED
Dale, LUNSPECIFIEDUNSPECIFIED
Schett, GUNSPECIFIEDUNSPECIFIED
Zwerina, JUNSPECIFIEDUNSPECIFIED
Eltawil, NUNSPECIFIEDUNSPECIFIED
Pitzalis, CUNSPECIFIEDUNSPECIFIED
Dell’Accio, FUNSPECIFIEDUNSPECIFIED
Date : 4 May 2016
Identification Number : https://doi.org/10.1136/annrheumdis-2015-208577
Copyright Disclaimer : This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Uncontrolled Keywords : Chondrocytes, Knee Osteoarthritis, Osteoarthritis
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 14:41
Last Modified : 04 Jul 2017 16:59
URI: http://epubs.surrey.ac.uk/id/eprint/813868

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