WISP-2 modulates the induction of inflammatory mediators and cartilage catabolism in chondrocytes.

Feb 13, 2023

Experts: Clara Ruiz-Fernández,María González-Rodríguez,Vanessa Abella,Vera Francisco,Alfonso Cordero-Barreal,Djedjiga Ait Eldjoudi,Yousof Farrag,Jesús Pino,Javier Conde-Aranda,Miguel Ángel González-Gay,Antonio Mera,Ali Mobasheri,Lucía García-Caballero,Marina Gándara-Cortés,Francisca Lago,Morena Scotece,Oreste Gualillo

Wnt-1 inducible signaling pathway protein 2 (WISP-2/CCN5) is a recently identified adipokine that has been described as an important mediator of canonical Wnt activation in adipogenic precursor cells. In osteoarthritis (OA), the most common form of arthritis, chondrocytes exhibit aberrant and increased production of pro-inflammatory mediators and matrix degrading enzymes such as IL-1β and MMP-13. Although recent evidence suggests a role for Wnt signaling in OA physiopathology, little is known about the involvement of WISP-2 in cartilage degradation. In the present study, we determined the expression of WISP-2 in healthy and OA human chondrocytes. WISP-2 expression is modulated along chondrocyte differentiation and downregulated at the onset of hypertrophy by inflammatory mediators. We also investigated the effect of WISP-2 on cartilage catabolism and performed WISP-2 loss-of-function experiments using RNA interference technology in human T/C-28a2 immortalized chondrocytes. We demonstrated that recombinant human WISP-2 protein reduced IL-1β-mediated chondrocyte catabolism, that IL-1β and WNT/b-catenin signaling pathways are involved in rhWISP-2 protein and IL-1β effects in human chondrocytes, and that WISP-2 has a regulatory role in attenuating the catabolic effects of IL-1β in chondrocytes. Gene silencing of WISP-2 increased the induction of the catabolic markers MMP-13 and ADAMTS-5 and the inflammatory mediators IL-6 and IL-8 triggered by IL-1β in human primary OA chondrocytes in a Wnt/β-catenin dependent manner. In conclusion, here we have shown for the first time that WISP-2 may have relevant roles in modulating the turnover of extracellular matrix in the cartilage and that its downregulation may detrimentally alter the inflammatory environment in OA cartilage. We also proved the participation of Wnt/β-catenin signaling pathway in these processes. Thus, targeting WISP-2 might represent a potential therapeutical approach for degenerative and/or inflammatory diseases of musculoskeletal system, such as osteoarthritis.
Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.

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ABOUT THE EXPERTS

Clara Ruiz-Fernández,María González-Rodríguez,Vanessa Abella,Vera Francisco,Alfonso Cordero-Barreal,Djedjiga Ait Eldjoudi,Yousof Farrag,Jesús Pino,Javier Conde-Aranda,Miguel Ángel González-Gay,Antonio Mera,Ali Mobasheri,Lucía García-Caballero,Marina Gándara-Cortés,Francisca Lago,Morena Scotece,Oreste Gualillo

Clara Ruiz-Fernández

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain; International PhD School of the University of Santiago de Compostela (EDIUS), Doctoral Programme in Medicine Clinical Research, Santiago de Compostela, Spain.

María González-Rodríguez

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain; International PhD School of the University of Santiago de Compostela (EDIUS), Doctoral Programme in Drug Research and Development, Santiago de Compostela, Spain.

Vanessa Abella

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain.

Vera Francisco

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain.

Alfonso Cordero-Barreal

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain.

Djedjiga Ait Eldjoudi

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain.

Yousof Farrag

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain.

Jesús Pino

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain.

Javier Conde-Aranda

Molecular and Cellular Gastroenterology Group, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain.

Miguel Ángel González-Gay

Hospital Universitario Marqués de Valdecilla, Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, University of Cantabria, Avenida de Valdecilla s/n, Santander, Cantabria, Spain.

Antonio Mera

SERGAS, Santiago University Clinical Hospital, Division of Rheumatology, Santiago de Compostela, Spain.

Ali Mobasheri

Research Unit of Medical Imaging, Physics, and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania; University Medical Center Utrecht, Departments of Orthopedics, Rheumatology and Clinical Immunology, Utrecht, The Netherlands; Department of Joint Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Lucía García-Caballero

Department of Morphological Sciences. School of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain.

Marina Gándara-Cortés

Department of Morphological Sciences. School of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain.

Francisca Lago

SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), Molecular and Cellular Cardiology Lab, Research Laboratory 7, Santiago University Clinical Hospital, Santiago de Compostela, Spain.

Morena Scotece

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain. Electronic address: morenascotece@gmail.com.

Oreste Gualillo

SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain. Electronic address: oreste.gualillo@sergas.es.