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Osteoarthritis: From Pathophysiology to Novel Therapy

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Guest Editor
Department of Biomedical Science, Cardenal Herrera-CEU University, 46115 Valencia, Spain
Interests: inflammation; immunology; cell biology

Special Issue Information

Dear Colleagues,

In the context of an ageing world population, certain pathologies that are exacerbated in this process of ageing, such as osteoarthritis (OA), will become more prevalent in the coming years. Moreover, OA is one of the main causes of chronic pain and physical disability in the elderly. It is therefore of great relevance to gain a deep understanding on the pathophysiology of this disease, and also to identify potential prognostic and diagnostic tools along with novel promising therapeutic targets for OA. 

This Special Issue will focus on the factors and molecular mechanisms that may be involved in the origin and progression of OA, as well as in the identification of novel therapeutic approaches. We welcome the submission of original articles, both basic and translational research papers, as well as review papers.

Dr. Paloma Guillem-Llobat
Guest Editor

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Keywords

  • osteoarthritis
  • therapeutic targets
  • molecular mechanisms
  • biomarkers
  • bone degenerative disease

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Published Papers (3 papers)

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Research

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23 pages, 1563 KB  
Article
Synovial Fluid and Serum MicroRNA Signatures in Equine Osteoarthritis
by Catarina I. G. D. Castanheira, Sarah Taylor, Eva Skiöldebrand, Luis M. Rubio-Martinez, Matthias Hackl, Peter D. Clegg and Mandy J. Peffers
Int. J. Mol. Sci. 2025, 26(22), 11190; https://doi.org/10.3390/ijms262211190 - 19 Nov 2025
Cited by 1 | Viewed by 845
Abstract
The aim of this study was to identify differentially expressed microRNAs (miRNAs) in serum and synovial fluid (SF) samples of control horses and those with osteoarthritis (OA) to identify potential candidates for biomarkers of disease. Total RNA was extracted from serum and SF [...] Read more.
The aim of this study was to identify differentially expressed microRNAs (miRNAs) in serum and synovial fluid (SF) samples of control horses and those with osteoarthritis (OA) to identify potential candidates for biomarkers of disease. Total RNA was extracted from serum and SF samples of control (n = 4) and OA (n = 9) horses and sequenced. Differential expression analysis, pathway analysis and miRNA target prediction were performed. A group of six miRNAs (eca-miR-199a-3p, eca-miR-148a, eca-miR-99b, eca-miR-146a, eca-miR-423-5p and eca-miR-23b) was selected for validation in an independent cohort (serum, n = 46; SF, n = 88). The effect of clinical variables on miRNA expression was also assessed. Sequencing analyses found 43 and 23 differentially expressed miRNAs in serum and SF samples, respectively. Pathway analysis showed miRNAs were involved in inflammatory disease/response and associated with OA pathways. miRNA expression in serum was strongly associated with the horses’ workload, while age had a pronounced influence on miRNA expression in SF. Distinct patterns of miRNA differential expression were observed in serum and SF samples from horses with OA compared to controls. miR-199a-3p and miR-148a warrant further investigation as potential biomarkers of equine OA. Further characterization of these molecular changes could provide novel insights into the mechanisms of early OA. Full article
(This article belongs to the Special Issue Osteoarthritis: From Pathophysiology to Novel Therapy)
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Review

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16 pages, 1410 KB  
Review
Exosomes and Small Extracellular Vesicles as an Alternative to Mesenchymal Stromal Cell Therapy in Knee Osteoarthritis: From Biological Rationale to Clinical Evidence
by Mahdi Al-Jeabory, Jaroslaw Pecold, Maciej Maslyk, Michal Pruc, Karolina Gromek, Robert Weglowski and Lukasz Szarpak
Int. J. Mol. Sci. 2026, 27(9), 3737; https://doi.org/10.3390/ijms27093737 - 23 Apr 2026
Viewed by 211
Abstract
Knee osteoarthritis (KOA) is a leading cause of pain and disability worldwide, and current treatments remain largely symptomatic, with no disease-modifying therapy established for routine use. This narrative review evaluates extracellular vesicles (EVs) as biological nanocarriers and a cell-free alternative to mesenchymal stromal [...] Read more.
Knee osteoarthritis (KOA) is a leading cause of pain and disability worldwide, and current treatments remain largely symptomatic, with no disease-modifying therapy established for routine use. This narrative review evaluates extracellular vesicles (EVs) as biological nanocarriers and a cell-free alternative to mesenchymal stromal cell therapy for KOA by examining the biological rationale, preclinical evidence, clinical studies, and current methodological and regulatory requirements. Preclinical findings indicate that EVs may exert immunomodulatory, anti-inflammatory, and chondroprotective effects, supporting their potential to influence joint homeostasis. The review also summarizes current recommendations for EV nomenclature, characterization, and quality control in accordance with the Minimal Information for Studies of EVs 2023 guidelines and highlights key translational challenges, including scalable manufacturing, potency assessment, and regulatory compliance. Clinical evidence to date suggests a favorable safety profile, but efficacy data remain limited and inconsistent; a randomized placebo-controlled trial showed no superiority over placebo, whereas small early human studies suggested possible benefit in selected cases. Overall, EVs represent a promising cell-free strategy for KOA, but current evidence is insufficient to support routine clinical use, emphasizing the need for standardized production, validated potency assays, and robust randomized clinical trials. Full article
(This article belongs to the Special Issue Osteoarthritis: From Pathophysiology to Novel Therapy)
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22 pages, 1039 KB  
Review
Epigenetic Biomarkers in Temporomandibular Joint Osteoarthritis: An Emerging Target in Treatment
by Schilin Wen, Javiera Santander, Daniel Barria, Luis A. Salazar, Cristian Sandoval, Consuelo Arias and Verónica Iturriaga
Int. J. Mol. Sci. 2025, 26(8), 3668; https://doi.org/10.3390/ijms26083668 - 12 Apr 2025
Cited by 2 | Viewed by 2782
Abstract
Osteoarthritis (OA) of the temporomandibular joint (TMJ) is a progressive disease characterized by the progressive destruction of the internal surfaces of the joint. Certain epigenetic biomarkers have been detected in TMJ-OA. We summarized the available evidence on the epigenetic biomarkers in TMJ-OA. There [...] Read more.
Osteoarthritis (OA) of the temporomandibular joint (TMJ) is a progressive disease characterized by the progressive destruction of the internal surfaces of the joint. Certain epigenetic biomarkers have been detected in TMJ-OA. We summarized the available evidence on the epigenetic biomarkers in TMJ-OA. There is an increase in the expression of non-coding RNAs related to the degradation of the extracellular matrix, chondrocyte apoptosis, and proinflammatory cytokines, while there is a decrease in the expression of those related to COL2A1, as well as the osteogenic and chondrogenic differentiation of mesenchymal stem cells. Certain methylated genes and histone modifications in TMJ-OA were also identified. In the early stage, DNA methylation was significantly decreased; that is, the expression of inflammation-related genes such as TNF and genes associated with extracellular matrix degradation, such as Adamts, were increased. While in the late stage, there was an increase in the expression of genes associated with the TGF-β and MAPK signaling pathway and angiogenesis-related genes. Although research on the role of epigenetic markers in TMJ-OA is still ongoing, the results here contribute to improving the basis for the identification of accurate diagnostic and prognostic markers and the development of new therapeutic molecules for the prevention and management of TMJ-OA. It also represents a significant advancement in elucidating its pathogenesis. Full article
(This article belongs to the Special Issue Osteoarthritis: From Pathophysiology to Novel Therapy)
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