Paisan M, Papadopoulos KI, Papadopoulou A, Prasongchean W, Wattanaarsakit P. Intertwined roles of microRNA-155 and metformin in osteoarthritis: Novel potential diagnostic, prognostic, and therapeutic modulators. World J Orthop 2025; 16(12): 110992 [DOI: 10.5312/wjo.v16.i12.110992]
Corresponding Author of This Article
Konstantinos I Papadopoulos, MD, PhD, Department of Research and Development, THAI StemLife, 566/3 THAI StemLife Bldg, Soi Ramkhamhaeng 39 (Thepleela 1), Prachaouthit Road, Wangthonglang, Bangkok 10330, Thailand. kostas@thaistemlife.co.th
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Orthopedics
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Review
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 18, 2025 (publication date) through Dec 17, 2025
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World Journal of Orthopedics
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2218-5836
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Paisan M, Papadopoulos KI, Papadopoulou A, Prasongchean W, Wattanaarsakit P. Intertwined roles of microRNA-155 and metformin in osteoarthritis: Novel potential diagnostic, prognostic, and therapeutic modulators. World J Orthop 2025; 16(12): 110992 [DOI: 10.5312/wjo.v16.i12.110992]
World J Orthop. Dec 18, 2025; 16(12): 110992 Published online Dec 18, 2025. doi: 10.5312/wjo.v16.i12.110992
Intertwined roles of microRNA-155 and metformin in osteoarthritis: Novel potential diagnostic, prognostic, and therapeutic modulators
Mantana Paisan, Konstantinos I Papadopoulos, Alexandra Papadopoulou, Weerapong Prasongchean, Phanphen Wattanaarsakit
Mantana Paisan, Konstantinos I Papadopoulos, Department of Research and Development, THAI StemLife, Bangkok 10330, Thailand
Alexandra Papadopoulou, Department of Occupational and Environmental Health Services, Feelgood Lund, Lund 223-63, Skane, Sweden
Weerapong Prasongchean, General Education Center, Chulalongkorn University, Bangkok 10330, Thailand
Phanphen Wattanaarsakit, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
Author contributions: Paisan M conceived and conceptualized the pathophysiology, designed the review, screened articles obtained through the literature search, drafted the initial manuscript, and reviewed and revised the manuscript; Papadopoulos KI performed the literature search, extracted vital information, contributed to the synthesis of the review, and reviewed and revised the manuscript; Papadopoulou A and Prasongchean W equally assisted in the literature search, aided in extracting additional information and reviewed and revised the manuscript; Wattanaarsakit P coordinated and supervised the literature search, made substantial and direct intellectual contributions, and critically reviewed the manuscript for important intellectual content; all authors approved the submitted final manuscript and agree to be accountable for all aspects of the work.
Conflict-of-interest statement: The authors report no conflicts of interest and have nothing to disclose.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Konstantinos I Papadopoulos, MD, PhD, Department of Research and Development, THAI StemLife, 566/3 THAI StemLife Bldg, Soi Ramkhamhaeng 39 (Thepleela 1), Prachaouthit Road, Wangthonglang, Bangkok 10330, Thailand. kostas@thaistemlife.co.th
Received: June 20, 2025 Revised: July 20, 2025 Accepted: October 20, 2025 Published online: December 18, 2025 Processing time: 180 Days and 15.2 Hours
Abstract
Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degradation, synovial inflammation, and subchondral bone remodelling. Despite its increasing prevalence, effective diagnostic, disease-limiting, and therapeutic strategies remain unattainable. Recent studies have recognized the involvement of microRNA-155 (miR-155) in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression. MiR-155, a key endogenous regulator of the immune system, mechano-transduction, and multiple genetic pathways, interacts with OA targets of cellular energetic and circadian homeostasis, promoting systemic and local articular inflammation, cartilage matrix degradation, and chondrocyte apoptosis. Metformin, widely used for type 2 diabetes, has demonstrated anti-inflammatory, anti-oxidative, and chondroprotective properties in OA, mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling. Enthrallingly, metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation, indicating synergistic, potentially disease-modifying effects in OA. This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression. MiR-155 targeting – through microRNA therapeutics (mimics/antagomiRs) and/or metformin – could pave the way for innovative treatments, including novel articular delivery systems and cell-based therapies.
Core Tip: In osteoarthritis (OA) and its associated risk factors, elevated microRNA-155 (miR-155) regulates systemic and local joint inflammatory mediators, extracellular matrix degradation, and chondrocyte apoptosis, with context-dependent roles in cartilage repair. MiR-155 also shows promise as a diagnostic and prognostic biomarker. Metformin exerts cartilage-protective effects via adenosine monophosphate-activated protein kinase activation, nuclear factor kappa-B inhibition, and possible modulation of miR-155 expression. Combined miR-155-targeted strategies and metformin in OA could enhance anti-inflammation, cartilage-preservation, and joint regeneration through the development of innovative treatments, including novel articular delivery systems and cell-based therapies. Further research is needed to fully understand the molecular underpinnings of this relationship.
