University of Oulu

Kovács P, Pushparaj PN, Takács R, Mobasheri A and Matta C (2023) The clusterin connectome: Emerging players in chondrocyte biology and putative exploratory biomarkers of osteoarthritis. Front. Immunol. 14:1103097. doi: 10.3389/fimmu.2023.1103097

The clusterin connectome : emerging players in chondrocyte biology and putative exploratory biomarkers of osteoarthritis

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Author: Kovács, Patrik1; Pushparaj, Peter Natesan2,3; Takács, Roland1;
Organizations: 1Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
2Center of Excellence in Genomic Medicine Research (CEGMR), Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
3Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, India
4FibroHealth Interdisciplinary Research Programme, Fibrobesity Cluster, Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
5Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
6Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
7World 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, 2.6 MB)
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Language: English
Published: Frontiers Media, 2023
Publish Date: 2023-08-14


Introduction: Clusterin is a moonlighting protein that has many functions. It is a multifunctional holdase chaperone glycoprotein that is present intracellularly and extracellularly in almost all bodily fluids. Clusterin is involved in lipid transport, cell differentiation, regulation of apoptosis, and clearance of cellular debris, and plays a protective role in ensuring cellular survival. However, the possible involvement of clusterin in arthritic disease remains unclear. Given the significant potential of clusterin as a biomarker of osteoarthritis (OA), a more detailed analysis of its complex network in an inflammatory environment, specifically in the context of OA, is required. Based on the molecular network of clusterin, this study aimed to identify interacting partners that could be developed into biomarker panels for OA.

Methods: The STRING database and Cytoscape were used to map and visualize the clusterin connectome. The Qiagen Ingenuity Pathway Analysis (IPA) software was used to analyze and study clusterin associated signaling networks in OA. We also analyzed transcription factors known to modulate clusterin expression, which may be altered in OA.

Results: The top hits in the clusterin network were intracellular chaperones, aggregate-forming proteins, apoptosis regulators and complement proteins. Using a text-mining approach in Cytoscape, we identified additional interacting partners, including serum proteins, apolipoproteins, and heat shock proteins.

Discussion: Based on known interactions with proteins, we predicted potential novel components of the clusterin connectome in OA, including selenoprotein R, semaphorins, and meprins, which may be important for designing new prognostic or diagnostic biomarker panels.

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Series: Frontiers in immunology
ISSN: 1664-3224
ISSN-E: 1664-3224
ISSN-L: 1664-3224
Volume: 14
Article number: 1103097
DOI: 10.3389/fimmu.2023.1103097
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
3111 Biomedicine
Funding: CM and PK were supported by the Young Researcher Excellence Program (grant number: FK-134304) of the National Research, Development, and Innovation Office, Hungary. Project no. TKP2020-NKA-04 was implemented with support provided by the National Research, Development, and Innovation Fund of Hungary, financed under the 2020-4.1.1-TKP2020 funding scheme. AM acknowledges financial support from the Academy of Finland through the Profi6 336449 grant awarded to the University of Oulu, the European Commission Horizon Health programme and the PROTO Consortium, (Grant agreement ID: 101095635, and 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). CM, AM and RT also acknowledge financial support from the European Cooperation in Science and Technology COST Association Action CA21110 - Building an open European Network on OsteoArthritis research (NetwOArk); PNP acknowledges the financial support from the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia, through project number (1045).
Copyright information: © 2023 Kovács, Pushparaj, Takács, Mobasheri and Matta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.