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Post-traumatic osteoarthritis development is not modified by postnatal chondrocyte deletion of Ccn2

Keenan, CM; Ramos-Mucci, L; Kanakis, I; Milner, PI; Leask, A; Abraham, D; Bou-Gharios, G; (2020) Post-traumatic osteoarthritis development is not modified by postnatal chondrocyte deletion of Ccn2. Disease Models & Mechanisms , 13 (7) , Article dmm044719. 10.1242/dmm.044719. Green open access

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Abstract

CCN2 is a matricellular protein involved in several critical biological processes. In particular, CCN2 is involved in cartilage development and in osteoarthritis. CCN2 null mice exhibit a range of skeletal dysmorphisms, highlighting its importance in regulating matrix formation during development, however its role in adult cartilage remains unclear. The aim of this study was to determine the role of CCN2 in postnatal chondrocytes in models of post-traumatic osteoarthritis (PTOA). CCN2 deletion was induced in articular chondrocytes of male transgenic mice at 8 weeks of age. PTOA was induced in knees either surgically or non-invasively by repetitive mechanical loading at 10 weeks of age. Knee joints were harvested, scanned with micro-computed tomography and processed for histology. Sections were stained with toluidine blue and scored using the OARSI grading system. In the non-invasive model cartilage lesions were present in the lateral femur but no significant differences were observed between wildtype (WT) and CCN2 knockout (KO) mice 6 weeks post-loading. In the surgical model, severe cartilage degeneration was observed in the medial compartments but no significant differences were observed between WT and CCN2 KO mice at 2, 4, and 8 weeks post-surgery. We conclude that CCN2 deletion in chondrocytes did not modify the development of PTOA in mice, suggesting that chondrocyte expression of CCN2 in adults is not a critical player in protecting cartilage from the degeneration associated with PTOA.

Type: Article
Title: Post-traumatic osteoarthritis development is not modified by postnatal chondrocyte deletion of Ccn2
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dmm.044719
Publisher version: https://doi.org/10.1242/dmm.044719
Language: English
Additional information: Copyright © 2020. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: CCN2, Cartilage, Osteoarthritis, Post-traumatic, Transgenic mouse, Trauma-induced
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10105376
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