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Research Paper|Volume 12, Issue 11|pp 10129—10146

Clusterin exerts a cytoprotective and antioxidant effect in human osteoarthritic cartilage

Chiara Tarquini1,2, Sabina Pucci1, Maria Giovanna Scioli1, Elena Doldo1, Sara Agostinelli1, Federico D’Amico1, Alessandra Bielli1, Amedeo Ferlosio1, Emanuele Caredda3, Umberto Tarantino2, Augusto Orlandi1,4
  • 1Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
  • 2Orthopedics and Traumatology, Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy
  • 3Hygiene and Preventive Medicine, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
  • 4Department of Biomedical Sciences, Catholic University Our Lady of Good Counsel, Tirana, Albania
* Co-first authors
# Co-last authors
Received: January 16, 2020Accepted: April 28, 2020Published: June 9, 2020
https://doi.org/10.18632/aging.103310

Copyright © 2020 Tarquini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Osteoarthritis (OA) is the most common joint disease characterized by destruction of articular cartilage. OA-induced cartilage degeneration causes inflammation, oxidative stress and the hypertrophic shift of quiescent chondrocytes. Clusterin (CLU) is a ubiquitous glycoprotein implicated in many cellular processes and its upregulation has been recently reported in OA cartilage. However, the specific role of CLU in OA cartilage injury has not been investigated yet. We analyzed CLU expression in human articular cartilage in vivo and in cartilage-derived chondrocytes in vitro. CLU knockdown in OA chondrocytes was also performed and its effect on proliferation, hypertrophic phenotype, apoptosis, inflammation and oxidative stress was investigated. CLU expression was upregulated in human OA cartilage and in cultured OA cartilage-derived chondrocytes compared with control group. CLU knockdown reduced cell proliferation and increased hypertrophic phenotype as well as apoptotic death. CLU-silenced OA chondrocytes showed higher MMP13 and COL10A1 as well as greater TNF-α, Nox4 and ROS levels. Our results indicate a possible cytoprotective role of CLU in OA chondrocytes promoting cell survival by its anti-apoptotic, anti-inflammatory and antioxidant properties and counteracting the hypertrophic phenotypic shift. Further studies are needed to deepen the role of CLU in order to identify a new potential therapeutic target for OA.