AccScience Publishing / JCTR / Online First / DOI: 10.36922/JCTR025370062
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ORIGINAL ARTICLE

Unveiling the role of ubiquitin-specific protease family in osteoporosis: A focus on USP17L2 and USP19

Seyedeh Zahra Mousavi1 ,  Nasrin Payab2 ,  Mohammad Sina3 ,  Elham Tootoonchi4 ,  Amirhossein Ghorbanpour5 ,  Morteza Dehghan6 ,  Razieh Pourahmad Jaktaji7 ,  Morteza Hadizadeh8*
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1 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
2 Department of Biochemistry, Faculty of Sciences, Shahrekord University, Shahrekord, Chaharmahal and Bakhtiari, Iran
3 Department of Molecular and Translational Medicine, Angelo Nocivelli Institute for Molecular Medicine, University of Brescia, Brescia, Lombardy, Italy
4 Medical Genetics and Molecular Biology Research Hub, Royan TuCAGene Ltd., Tehran, Iran
5 Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
6 Department of Orthopedics, School of Medicine, Kashani Hospital, Shahrekord University of Medical Sciences, Shahrekord, Chaharmahal and Bakhtiari, Iran
7 Department of Genetics, Faculty of Sciences, Shahrekord University, Shahrekord, Chaharmahal and Bakhtiari, Iran
8 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
JCTR, 025370062 https://doi.org/10.36922/JCTR025370062
Received: 14 September 2025 | Revised: 18 January 2026 | Accepted: 22 April 2026 | Published online: 5 June 2026
(This article belongs to the Special Issue Biomedicine and Bioinformatics Engineering )
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Background: The ubiquitin-proteasome system is vital for regulating protein stability and function, influencing numerous cellular processes, including bone homeostasis. Aim: This study aims to uncover the role of the ubiquitin-specific protease (USP) family in osteoporosis. Methods: The osteoporosis expression microarray profile was analyzed to identify differentially expressed genes (DEGs). DEGs related to ubiquitins were isolated, followed by the analysis of biological pathways and gene ontology for these genes. The interactions between differentially expressed ubiquitins (DE-Ubs) and their targets were examined using the UbiBrowser database. Ultimately, a network of interactions between DE-Ubs and their targets in the context of osteoporosis was constructed. The diagnostic potential of the DE-Ubs was evaluated using receiver operating characteristic (ROC) analysis. Additionally, antisense oligonucleotide design and validation were performed using various bioinformatics tools, including Sfold, IDT OligoAnalyzer, RNAfold, RNAhybrid, and HNADOCK. Results: Among the 1,082 DEGs, USP19 and USP17L2 were recognized as statistically significant due to their involvement in the mitogen-activated protein kinase and Ras signaling pathways. The diagnostic potential of USP19 as a biomarker was confirmed through ROC analysis, demonstrating its high predictive accuracy in osteoporosis. Among the designed antisense oligonucleotides for USP19, the sequence TGTCACGCCAGATAAAACTA showed the most favorable predicted properties according to the ΔG values and structural stability. Conclusion: This study provides insights into the USP family genes associated with osteoporosis and identifies potential therapeutic targets for further investigation. Relevance for patients: This study identifies USP19 as a promising biomarker for early osteoporosis detection.

Keywords
USP19
USP17L2
Antisense oligonucleotides
Osteoporosis
Protein– protein interaction
Funding
None.
Conflict of interest
The authors declare no conflict of interest.
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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing
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