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Osteoarthritis 3.0: From Molecular Pathways to Therapeutic Advances
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Osteoarthritis 3.0: From Molecular Pathways to Therapeutic Advances

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 20 March 2025 | Viewed by 15672

Special Issue Editor

Dr. Nicola Veronese

E-Mail Website
Guest Editor
Geriatrics Section, Department of Internal Medicine, University of Palermo, 90133 Palermo, Italy
Interests: nutrition; epidemiology; older people; magnesium
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Osteoarthritis (OA) is an epidemiologically relevant age-related disorder that commonly affects the synovial joints, culminating in the irreversible destruction of the articular cartilage. OA is the most common musculoskeletal condition, particularly patients of an advanced age, but its exact etiology remains unclear.

In this regard, inflammation appears to be a relevant pathway involved in the etiology of OA; however, OA is most commonly a degenerative condition, not an inflammatory condition. Moreover, it seems that the apoptosis of the cells in the articular cartilage could be important, but research studying this idea is still limited to a few in vitro experiments. Finally, the molecular pathways involved in the therapeutic approaches used in OA are still inadequately researched.

As volumes 1 and 2 of the Special Issue “Osteoarthritis: From Molecular Pathways to Therapeutic Advances” have been successful, we will be exploring this issue further in International Journal of Molecular Sciences (ISSN 1422-0067, IF 6.208, JCR Category Q1). In this third Special Issue, we are inviting contributions of original research papers, mini and full reviews, and perspectives that address the progress and current knowledge of the pathophysiological mechanisms of OA, particularly those regarding molecular explanations of the etiology of OA. This Special Issue will also include therapeutic pharmacological and cell-based strategies, including stem cell therapy, to improve the treatment outcomes of OA. The published Special Issues can be found at the following links:

https://www.mdpi.com/journal/ijms/special_issues/Osteoarthritis_2020

https://www.mdpi.com/journal/ijms/special_issues/Osteoarthritis_2022

Dr. Nicola Veronese
Guest Editor

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Keywords

  • osteoarthritis
  • inflammation
  • pathophysiology of osteoarthritis (OA)
  • pharmacology
  • biomarkers for osteoarthritis

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Published Papers (6 papers)

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Research

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21 pages, 2402 KiB  
Article
MicroRNA as Possible Mediators of the Synergistic Effect of Celecoxib and Glucosamine Sulfate in Human Osteoarthritic Chondrocyte Exposed to IL-1β
by Sara Cheleschi, Nicola Veronese, Serafino Carta, Giulia Collodel, Maria Bottaro, Elena Moretti, Roberta Corsaro, Marcella Barbarino and Antonella Fioravanti
Int. J. Mol. Sci. 2023, 24(19), 14994; https://doi.org/10.3390/ijms241914994 - 8 Oct 2023
Cited by 1 | Viewed by 1697
Abstract
This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for [...] Read more.
This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for 24 h, with or without interleukin (IL)-1β (10 ng/mL). Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis and reactive oxygen species (ROS) by cytometry, nitric oxide (NO) by Griess method. Gene levels of miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2, and B-cell lymphoma (BCL)2 expressions were analyzed by quantitative real time polymerase chain reaction (real time PCR). Protein expression of NRF2 and BCL2 was also detected at immunofluorescence and western blot. Celecoxib and GS, alone or in combination, significantly increased viability, reduced apoptosis, ROS and NO production and the gene expression of miR-34a, -146a, -181a, -210, in comparison to baseline and to IL-1β. The transfection with miRNA specific inhibitors significantly counteracted the IL-1β activity and potentiated the properties of celecoxib and GS on viability, apoptosis and oxidant system, through nuclear factor (NF)-κB regulation. The observed effects were enhanced when the drugs were tested in combination. Our data confirmed the synergistic anti-inflammatory and chondroprotective properties of celecoxib and GS, suggesting microRNA as possible mediators. Full article
(This article belongs to the Special Issue Osteoarthritis 3.0: From Molecular Pathways to Therapeutic Advances)
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18 pages, 6314 KiB  
Article
Modulation of miR-146b Expression during Aging and the Impact of Physical Activity on Its Expression and Chondrogenic Progenitors
by Luca Dalle Carbonare, Arianna Minoia, Michele Braggio, Jessica Bertacco, Francesca Cristiana Piritore, Sharazed Zouari, Anna Vareschi, Rossella Elia, Ermes Vedovi, Cristina Scumà, Matilde Carlucci, Lekhana Bhandary, Monica Mottes, Maria Grazia Romanelli and Maria Teresa Valenti
Int. J. Mol. Sci. 2023, 24(17), 13163; https://doi.org/10.3390/ijms241713163 - 24 Aug 2023
Cited by 1 | Viewed by 1285
Abstract
The finding of molecules associated with aging is important for the prevention of chronic degenerative diseases and for longevity strategies. MicroRNAs (miRNAs) are post-transcriptional regulators involved in many biological processes and miR-146b-5p has been shown to be involved in different degenerative diseases. However, [...] Read more.
The finding of molecules associated with aging is important for the prevention of chronic degenerative diseases and for longevity strategies. MicroRNAs (miRNAs) are post-transcriptional regulators involved in many biological processes and miR-146b-5p has been shown to be involved in different degenerative diseases. However, miR-146b-5p modulation has not been evaluated in mesenchymal stem cells (MSCs) commitment or during aging. Therefore, the modulation of miR-146b-5p in the commitment and differentiation of mesenchymal cells as well as during maturation and aging in zebrafish model were analyzed. In addition, circulating miR-146b-5p was evaluated in human subjects at different age ranges. Thus, the role of physical activity in the modulation of miR-146b-5p was also investigated. To achieve these aims, RT (real-time)-PCR, Western blot, cell transfections, and three-dimensional (3D) culture techniques were applied. Our findings show that miR-146b-5p expression drives MSCs to adipogenic differentiation and increases during zebrafish maturation and aging. In addition, miR-146b-5p expression is higher in females compared to males and it is associated with the aging in humans. Interestingly, we also observed that the physical activity of walking downregulates circulating miR-146b-5p levels in human females and increases the number of chondroprogenitors. In conclusion, miR-146b-5p can be considered an age-related marker and can represent a useful marker for identifying strategies, such as physical activity, aimed at counteracting the degenerative processes of aging. Full article
(This article belongs to the Special Issue Osteoarthritis 3.0: From Molecular Pathways to Therapeutic Advances)
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Review

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29 pages, 10481 KiB  
Review
Controlled Stimulus-Responsive Delivery Systems for Osteoarthritis Treatment
by Qianwen Ye, Mingshuo Zhang, Shuyue Li, Wenyue Liu, Chunming Xu, Yumei Li and Renjian Xie
Int. J. Mol. Sci. 2024, 25(21), 11799; https://doi.org/10.3390/ijms252111799 - 2 Nov 2024
Viewed by 1134
Abstract
Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide and imposes a considerable burden on patients and society due to its high prevalence and economic costs. The pathogenesis of OA is closely related to the progressive degradation of [...] Read more.
Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide and imposes a considerable burden on patients and society due to its high prevalence and economic costs. The pathogenesis of OA is closely related to the progressive degradation of articular cartilage and the accompany inflammation; however, articular cartilage itself cannot heal and modulate the inflammation due to the lack of nerves, blood vessels, and lymph-vessels. Therefore, reliable and effective methods to treat OA remain highly desired. Local administration of drugs or bioactive materials by intra-articular injection of the delivery system represents a promising approach to treat OA, especially considering the prolonged joint retention, cartilage or chondrocytes targeting, and stimuli-responsive release to achieve precision OA therapy. This article summarizes and discusses the advances in the currently used delivery systems (nanoparticle, hydrogel, liposome, and microsphere) and then focuses on their applications in OA treatment from the perspective of endogenous stimulus (redox reactions, pH, enzymes, and temperature) and exogenous stimulus (near-infrared, magnetic, and ultrasound)-responsive release. Finally, the challenges and potential future directions for the development of nano-delivery systems are summarized. Full article
(This article belongs to the Special Issue Osteoarthritis 3.0: From Molecular Pathways to Therapeutic Advances)
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15 pages, 743 KiB  
Review
Advances in Stem Cell-Based Therapies in the Treatment of Osteoarthritis
by Ye Chen, Rui-Juan Cheng, Yinlan Wu, Deying Huang, Yanhong Li and Yi Liu
Int. J. Mol. Sci. 2024, 25(1), 394; https://doi.org/10.3390/ijms25010394 - 28 Dec 2023
Cited by 4 | Viewed by 5598
Abstract
Osteoarthritis (OA) is a chronic, degenerative joint disease presenting a significant global health threat. While current therapeutic approaches primarily target symptom relief, their efficacy in repairing joint damage remains limited. Recent research has highlighted mesenchymal stem cells (MSCs) as potential contributors to cartilage [...] Read more.
Osteoarthritis (OA) is a chronic, degenerative joint disease presenting a significant global health threat. While current therapeutic approaches primarily target symptom relief, their efficacy in repairing joint damage remains limited. Recent research has highlighted mesenchymal stem cells (MSCs) as potential contributors to cartilage repair, anti-inflammatory modulation, and immune regulation in OA patients. Notably, MSCs from different sources and their derivatives exhibit variations in their effectiveness in treating OA. Moreover, pretreatment and gene editing techniques of MSCs can enhance their therapeutic outcomes in OA. Additionally, the combination of novel biomaterials with MSCs has shown promise in facilitating the repair of damaged cartilage. This review summarizes recent studies on the role of MSCs in the treatment of OA, delving into their advantages and exploring potential directions for development, with the aim of providing fresh insights for future research in this critical field. Full article
(This article belongs to the Special Issue Osteoarthritis 3.0: From Molecular Pathways to Therapeutic Advances)
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26 pages, 1219 KiB  
Review
Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis
by Emőke Horváth, Árpád Sólyom, János Székely, Előd Ernő Nagy and Horațiu Popoviciu
Int. J. Mol. Sci. 2023, 24(22), 16468; https://doi.org/10.3390/ijms242216468 - 17 Nov 2023
Cited by 12 | Viewed by 3718
Abstract
Osteoarthritis (OA) is a complex disease of whole joints with progressive cartilage matrix degradation and chondrocyte transformation. The inflammatory features of OA are reflected in increased synovial levels of IL-1β, IL-6 and VEGF, higher levels of TLR-4 binding plasma proteins and increased expression [...] Read more.
Osteoarthritis (OA) is a complex disease of whole joints with progressive cartilage matrix degradation and chondrocyte transformation. The inflammatory features of OA are reflected in increased synovial levels of IL-1β, IL-6 and VEGF, higher levels of TLR-4 binding plasma proteins and increased expression of IL-15, IL-18, IL-10 and Cox2, in cartilage. Chondrocytes in OA undergo hypertrophic and senescent transition; in these states, the expression of Sox-9, Acan and Col2a1 is suppressed, whereas the expression of RunX2, HIF-2α and MMP-13 is significantly increased. NF-kB, which triggers many pro-inflammatory cytokines, works with BMP, Wnt and HIF-2α to link hypertrophy and inflammation. Altered carbohydrate metabolism and the upregulation of GLUT-1 contribute to the formation of end-glycation products that trigger inflammation via the RAGE pathway. In addition, a glycolytic shift, increased rates of oxidative phosphorylation and mitochondrial dysfunction generate reactive oxygen species with deleterious effects. An important surveyor mechanism, the YAP/TAZ signaling system, controls chondrocyte differentiation, inhibits ageing by protecting the nuclear envelope and suppressing NF-kB, MMP-13 and aggrecanases. The inflammatory microenvironment and synthesis of key matrix components are also controlled by SIRT1 and mTORc. Senescent chondrocytes represent the functional end stage of hypertrophic differentiation and characteristically upregulate p16 and p21, but also a variety of inflammatory cytokines, chemokines and metalloproteinases, developing the senescence-associated secretory phenotype. Senolysis with dendrobin, miR29b-5p and other agents has been shown to be efficient under experimental conditions, and appears to be a promising tool for the treatment of OA, as it restores COL2A1 and aggrecan synthesis, suppressing NF-kB and destructive metalloproteinases. Full article
(This article belongs to the Special Issue Osteoarthritis 3.0: From Molecular Pathways to Therapeutic Advances)
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26 pages, 654 KiB  
Review
The Effects of Chronological Age on the Chondrogenic Potential of Mesenchymal Stromal Cells: A Systematic Review
by Antonia Vogt, Konstantinos Kapetanos, Neophytos Christodoulou, Dimitrios Asimakopoulos, Mark A. Birch, Andrew W. McCaskie and Wasim Khan
Int. J. Mol. Sci. 2023, 24(20), 15494; https://doi.org/10.3390/ijms242015494 - 23 Oct 2023
Cited by 1 | Viewed by 1537
Abstract
Tissue engineering and cell therapy for regenerative medicine have great potential to treat chronic disorders. In musculoskeletal disorders, mesenchymal stromal cells (MSCs) have been identified as a relevant cell type in cell and regenerative strategies due to their multi-lineage potential, although this is [...] Read more.
Tissue engineering and cell therapy for regenerative medicine have great potential to treat chronic disorders. In musculoskeletal disorders, mesenchymal stromal cells (MSCs) have been identified as a relevant cell type in cell and regenerative strategies due to their multi-lineage potential, although this is likely to be a result of their trophic and immunomodulatory effects on other cells. This PRISMA systematic review aims to assess whether the age of the patient influences the chondrogenic potential of MSCs in regenerative therapy. We identified a total of 3027 studies after performing a search of four databases, including Cochrane, Web of Science, Medline, and PubMed. After applying inclusion and exclusion criteria, a total of 14 papers were identified that were reviewed, assessed, and reported. Cell surface characterization and proliferation, as well as the osteogenic, adipogenic, and chondrogenic differentiation, were investigated as part of the analysis of these studies. Most included studies suggest a clear link between aged donor MSCs and diminished clonogenic and proliferative potential. Our study reveals a heterogeneous and conflicting range of outcomes concerning the chondrogenic, osteogenic, and adipogenic potential of MSCs in relation to age. Further investigations on the in vitro effects of chronological age on the chondrogenic potential of MSCs should follow the outcomes of this systematic review, shedding more light on this complex relationship. Full article
(This article belongs to the Special Issue Osteoarthritis 3.0: From Molecular Pathways to Therapeutic Advances)
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