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Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast‐derived ADAMTS‐7 and ‐12

Journal of cellular and molecular medicine, 2019-06, Vol.23 (6), p.3974-3983 [Peer Reviewed Journal]

2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. ;Copyright © 2019 Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine ;ISSN: 1582-1838 ;EISSN: 1582-4934 ;DOI: 10.1111/jcmm.14283 ;PMID: 30903650

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Title:
Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast‐derived ADAMTS‐7 and ‐12
Author: Pérez‐García, Selene ; Carrión, Mar ; Villanueva‐Romero, Raúl ; Hermida‐Gómez, Tamara ; Fernández‐Moreno, Mercedes ; Mellado, Mario ; Blanco, Francisco J. ; Juarranz, Yasmina ; Gomariz, Rosa P.
Subjects: ADAMTS Proteins - genetics ; ADAMTS Proteins - metabolism ; ADAMTS7 Protein - genetics ; ADAMTS7 Protein - metabolism ; ADAMTS‐12 ; ADAMTS‐7 ; Aged ; Arthritis ; Cartilage ; Cartilage - metabolism ; Cartilage - pathology ; Cartilage diseases ; Cartilage oligomeric matrix protein ; Cartilage Oligomeric Matrix Protein - genetics ; Cartilage Oligomeric Matrix Protein - metabolism ; Cbfa-1 protein ; COMP ; Core Binding Factor Alpha 1 Subunit - genetics ; Core Binding Factor Alpha 1 Subunit - metabolism ; Damage prevention ; Degradation ; Dkk1 protein ; Drug delivery ; Drug development ; Extracellular matrix ; Extracellular Matrix - drug effects ; Extracellular Matrix - genetics ; Extracellular Matrix - metabolism ; Female ; Fibroblasts ; Fibroblasts - metabolism ; Fibronectin ; Fibronectins - pharmacology ; Homeostasis ; Humans ; Inhibition ; Interleukin-1beta - pharmacology ; Knowledge management ; Male ; Matrix protein ; Original ; Osteoarthritis ; Osteoarthritis - genetics ; Osteoarthritis - metabolism ; Runx2 ; Signal transduction ; synovial fibroblasts ; Synovial Membrane - cytology ; Wnt protein ; Wnt Signaling Pathway - genetics ; Wnt signalling
Is Part Of: Journal of cellular and molecular medicine, 2019-06, Vol.23 (6), p.3974-3983
Description: Failure of therapeutic approaches for the treatment of osteoarthritis (OA) based on the inhibition of metalloproteinases, might be because of their constitutive expression in homeostasis, together with their network complexity. The knowledge of this network would contribute to selective target pathological conditions. In this sense, blockade of mediators produced by neighbouring joint cells, such as synovial fibroblasts (SF), would prevent cartilage damage. Thus, we studied the contribution of ADAMTS‐7 and ‐12 from SF to cartilage oligomeric matrix protein (COMP) degradation, and the signalling pathways involved in their expression. We report for the first time in SF, the involvement of ERK‐Runx2 axis and Wnt/β‐catenin signalling in ADAMTS‐12 and ADAMTS‐7 expressions, respectively, with the subsequent consequences in COMP degradation from cartilage extracellular matrix. After stimulation with IL‐1β or fibronectin fragments, we showed that ERK inhibition decreased Runx2 activation and ADAMTS‐12 expression in OA‐SF, also reducing Fn‐fs‐induced COMP degradation. Blockage of Wnt signalling by DKK1 reduced ADAMTS‐7 and COMP degradation in OA‐SF as well. In addition, Wnt7B expression was induced by IL‐1β and by itself, also increasing ADAMTS‐7. Our results could contribute to the development of disease‐modifying OA drugs targeting ADAMTS‐7 and ‐12 for the prevention of extracellular matrix components degradation like COMP.
Publisher: England: John Wiley & Sons, Inc
Language: English
Identifier: ISSN: 1582-1838
EISSN: 1582-4934
DOI: 10.1111/jcmm.14283
PMID: 30903650
Source: Journals@Ovid Open Access Journal Collection Rolling
MEDLINE
Wiley Open Access
PubMed Central
ProQuest Central
DOAJ Directory of Open Access Journals

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Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast‐derived ADAMTS‐7 and ‐12

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