University of Oulu

Ursule Kalvaityte, Csaba Matta, Eiva Bernotiene, Peter Natesan Pushparaj, Ata M. Kiapour, Ali Mobasheri, Exploring the translational potential of clusterin as a biomarker of early osteoarthritis, Journal of Orthopaedic Translation, Volume 32, 2022, Pages 77-84, ISSN 2214-031X,

Exploring the translational potential of clusterin as a biomarker of early osteoarthritis

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Author: Kalvaityte, Ursule1; Matta, Csaba2; Bernotiene, Eiva1;
Organizations: 1Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT, 08406, Vilnius, Lithuania
2Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, H, 4032, Hungary
3Center of Excellence in Genomic Medicine Research (CEGMR), Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
4Department of Orthopedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, 021115, USA
5Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, FI, 90014, Oulu, Finland
6Department of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 508, GA, Utrecht, the Netherlands
7Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China
8World Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, Université de Liège, Liège, Belgium
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
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Language: English
Published: Elsevier, 2022
Publish Date: 2022-05-18


Background: Clusterin (CLU; also known as apolipoprotein J) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation. It is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis. CLU has been proposed to protect cells from cytolysis by complement components and has been implicated in Alzheimer’s disease due to its ability to bind amyloid-β peptides and prevent aggregate formation in the brain. Recent studies suggest that CLU performs moonlighting functions. CLU exists in two major forms: an intracellular form and a secreted extracellular form. The intracellular form of CLU may suppress stress-induced apoptosis by forming complexes with misfolded proteins and facilitates their degradation. The secreted form of CLU functions as an extracellular chaperone that prevents protein aggregation.

Methods: In this review, we discuss the published literature on the biology of CLU in cartilage, chondrocytes, and other synovial joint tissues. We also review clinical studies that have examined the potential for using this protein as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA).

Results: Since CLU functions as an extracellular chaperone, we propose that it may be involved in cytoprotective functions in osteoarticular tissues. The secreted form of CLU can be measured in synovial and systemic fluids and may have translational potential as a biomarker of early repair responses in OA.

Conclusion: There is significant potential for investigating synovial and systemic CLU as biomarkers of OA. Future translational and clinical orthopaedic studies should carefully consider the diverse roles of this protein and its involvement in other comorbidities. Therefore, future biomarker studies should not correlate circulating CLU levels exclusively to the process of OA pathogenesis and progression. Special attention should be paid to CLU levels in synovial fluid.

The Translational potential of this article: There is significant potential for investigating synovial and systemic CLU as a predictive biomarker of osteoarthritis (OA) progression and response to novel treatments and interventions. Given that CLU plays diverse roles in other comorbidities such as rheumatoid arthritis (RA) and obesity, future translational and clinical orthopaedic biomarker studies should not directly correlate circulating CLU levels to the process of OA pathogenesis and progression. However, special attention should be paid to CLU levels in synovial fluid. The cytoprotective properties of CLU may support the implementation of regenerative strategies and new approaches for developing targeted therapeutics for OA.

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Series: Journal of orthopaedic translation
ISSN: 2214-031X
ISSN-E: 2214-0328
ISSN-L: 2214-031X
Volume: 32
Pages: 77 - 84
DOI: 10.1016/
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
1182 Biochemistry, cell and molecular biology
Funding: The funding bodies were not involved in the study design, data collection, analysis, and interpretation. The decision to submit the paper for publication was not influenced by any of the funding bodies. CM was supported by the Premium Postdoctoral Research Fellowship of the Eötvös Loránd Research Network (ELKH), and the Young Researcher Excellence Programme (grant number: FK-134304) of the National Research, Development and Innovation Office, Hungary. CM was also supported by the EFOP-3.6.3-VEKOP-16-2017-00009 project co-financed by the EU and the European Social Fund. Project no. TKP2020-NKA-04 was implemented with the support provided by the National Research, Development and Innovation Fund of Hungary, financed under the 2020–4.1.1-TKP2020 funding scheme. AM, EB and UK acknowledge financial support from the European Structural and Social Funds through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the Programme Attracting Foreign Researchers for Research Implementation, Grant No. 01.2.2-LMT-K-718-02-0022.
Copyright information: © 2021 Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society. This is an open access article under the CC BY-NC-ND license (