Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances

Special Issue Editors
Special Issue Information
Keywords
Published Papers

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: closed (31 December 2022) | Viewed by 35669

Share This Special Issue

Special Issue Editor

Prof. Dr. Nicola Veronese

E-Mail Website
Guest Editor

Department of Geriatric Medicine, University of Palermo, 90133 Palermo, Italy
Interests: epidemiology; geriatrics; magnesium; frailty; osteoarthritis
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 volume 1 of the Special Issue “Osteoarthritis: From Molecular Pathways to Therapeutic Advances” has been successful, we will be exploring this issue further in the International Journal of Molecular Sciences (ISSN 1422-0067, IF 5.923, JCR Category Q1). In this second 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. The Special Issue will also include therapeutic pharmacological and cell-based strategies, including stem cell therapy, to improve the treatment outcomes of OA. The current Special Issue can be found at the following website:

https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijms/special_issues/Osteoarthritis_2020

Prof. Dr. Nicola Veronese
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

Published Papers (12 papers)

Download All Papers

Research

Jump to: Review

21 pages, 5636 KiB

Open AccessArticle

Timing Expression of miR203a-3p during OA Disease: Preliminary In Vitro Evidence

by Viviana Costa, Marcello De Fine, Lavinia Raimondi, Daniele Bellavia, Aurora Cordaro, Valeria Carina, Riccardo Alessandro, Giovanni Pignatti, Milena Fini, Gianluca Giavaresi and Angela De Luca

Int. J. Mol. Sci. 2023, 24(5), 4316; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054316 - 21 Feb 2023

Viewed by 1206

Abstract

Osteoarthritis (OA) is a degenerative bone disease that involves the microenvironment and macroenvironment of joints. Progressive joint tissue degradation and loss of extracellular matrix elements, together with different grades of inflammation, are important hallmarks of OA disease. Therefore, the identification of specific biomarkers to distinguish the stages of disease becomes a primary necessity in clinical practice. To this aim, we investigated the role of miR203a-3p in OA progression starting from the evidence obtained by osteoblasts isolated from joint tissues of OA patients classified according to different Kellgren and Lawrence (KL) grading (KL ≤ 3 and KL > 3) and hMSCs treated with IL-1β. Through qRT-PCR analysis, it was found that osteoblasts (OBs) derived from the KL ≤ 3 group expressed high levels of miR203a-3p and low levels of ILs compared with those of OBs derived from the KL > 3 group. The stimulation with IL-1β improved the expression of miR203a-3p and the methylation of the IL-6 promoter gene, favoring an increase in relative protein expression. The gain and loss of function studies showed that the transfection with miR203a-3p inhibitor alone or in co-treatments with IL-1β was able to induce the expression of CX-43 and SP-1 and to modulate the expression of TAZ, in OBs derived from OA patients with KL ≤ 3 compared with KL > 3. These events, confirmed also by qRT-PCR analysis, Western blot, and ELISA assay performed on hMSCs stimulated with IL-1β, supported our hypothesis about the role of miR203a-3p in OA progression. The results suggested that during the early stage, miR203a-3p displayed a protective role reducing the inflammatory effects on CX-43, SP-1, and TAZ. During the OA progression the downregulation of miR203a-3p and consequently the upregulation of CX-43/SP-1 and TAZ expression improved the inflammatory response and the reorganization of the cytoskeleton. This role led to the subsequent stage of the disease, where the aberrant inflammatory and fibrotic responses determined the destruction of the joint. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Figure 1

23 pages, 4376 KiB

Open AccessArticle

Sensory Neuron-Specific Deletion of Tropomyosin Receptor Kinase A (TrkA) in Mice Abolishes Osteoarthritis (OA) Pain via NGF/TrkA Intervention of Peripheral Sensitization

by InSug O-Sullivan, Ranjan Kc, Gurjit Singh, Vaskar Das, Kaige Ma, Xin Li, Fackson Mwale, Gina Votta-Velis, Benjamin Bruce, Arivarasu Natarajan Anbazhagan, Andre J. van Wijnen and Hee-Jeong Im

Int. J. Mol. Sci. 2022, 23(20), 12076; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012076 - 11 Oct 2022

Cited by 4 | Viewed by 2002

Abstract

Tropomyosin receptor kinase A (TrkA/NTRK1) is a high-affinity receptor for nerve growth factor (NGF), a potent pain mediator. NGF/TrkA signaling elevates synovial sensory neuronal distributions in the joints and causes osteoarthritis (OA) pain. We investigated the mechanisms of pain transmission as to whether peripheral sensory neurons are linked to the cellular plasticity in the dorsal root ganglia (DRG) and are critical for OA hyperalgesia. Sensory neuron-specific deletion of TrkA was achieved by tamoxifen injection in 4-week-old TrkA^fl/fl;Na_V1.8^CreERT2 (Ntrk1 ^fl/fl;Scn10a^CreERT2) mice. OA was induced by partial medial meniscectomy (PMM) in 12-week-old mice, and OA-pain-related behavior was analyzed for 12 weeks followed by comprehensive histopathological examinations. OA-associated joint pain was markedly improved without cartilage protection in sensory-neuron-specific conditional TrkA knock-out (cKO) mice. Alleviated hyperalgesia was associated with suppression of the NGF/TrkA pathway and reduced angiogenesis in fibroblast-like synovial cells. Elevated pain transmitters in the DRG of OA-induced mice were significantly diminished in sensory-neuron-specific TrkA cKO and global TrkA cKO mice. Spinal glial activity and brain-derived neurotropic factor (BDNF) were significantly increased in OA-induced mice but were substantially eliminated by sensory-neuron-specific deletion. Our results suggest that augmentation of NGF/TrkA signaling in the joint synovium and the peripheral sensory neurons facilitate pro-nociception and centralized pain sensitization. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Figure 1

18 pages, 1813 KiB

Open AccessArticle

Synovial Fluid Regulates the Gene Expression of a Pattern of microRNA via the NF-κB Pathway: An In Vitro Study on Human Osteoarthritic Chondrocytes

by Sara Cheleschi, Sara Tenti, Sauro Lorenzini, Iole Seccafico, Stefano Barbagli, Elena Frati and Antonella Fioravanti

Int. J. Mol. Sci. 2022, 23(15), 8334; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158334 - 28 Jul 2022

Cited by 3 | Viewed by 1914

Abstract

Synovial fluid (SF) represents the primary source of nutrients of articular cartilage and is implicated in maintaining cartilage metabolism. We investigated the effects of SF, from patients with osteoarthritis (OA), rheumatoid arthritis (RA), and controls, on a pattern of microRNA (miRNA) in human OA chondrocytes. Cells were stimulated with 50% or 100% SF for 24 h and 48 h. Apoptosis and superoxide anion production were detected by cytometry; miRNA (34a, 146a, 155, 181a), cytokines, metalloproteinases (MMPs), type II collagen (Col2a1), antioxidant enzymes, B-cell lymphoma (BCL)2, and nuclear factor (NF)-κB by real-time PCR. The implication of the NF-κB pathway was assessed by the use of NF-κB inhibitor (BAY-11-7082). RA and OA SF up-regulated miR-34a, -146a, -155, -181a, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, MMP-1, MMP-13, and ADAMTs-5 gene expression, while it down-regulated Col2a1. Pathological SF also induced apoptosis, reduced viability, and decreased BCL2 mRNA, whereas it increased superoxide anions, the expression of antioxidant enzymes, p65 and p50 NF-κB. Opposite and positive results were obtained with 100% control SF. Pre-incubation with BAY-11-7082 counteracted SF effects on miRNA. We highlight the role of the SF microenvironment in regulating some miRNA involved in inflammation and cartilage degradation during OA and RA, via the NF-κB pathway. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Figure 1

17 pages, 5208 KiB

Open AccessArticle

Do Synovial Inflammation and Meniscal Degeneration Impact Clinical Outcomes of Patients Undergoing Arthroscopic Partial Meniscectomy? A Histological Study

by Eleonora Olivotto, Elisa Belluzzi, Assunta Pozzuoli, Augusto Cigolotti, Manuela Scioni, Steven R. Goldring, Mary B. Goldring, Pietro Ruggieri, Roberta Ramonda, Brunella Grigolo, Giovanni Trisolino and Marta Favero

Int. J. Mol. Sci. 2022, 23(7), 3903; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073903 - 31 Mar 2022

Cited by 8 | Viewed by 1755

Abstract

The menisci exert a prominent role in joint stabilization and in the distribution of mechanical loading. Meniscal damage is associated with increased risk of knee OA. The aim of this study was to characterize the synovial membrane and meniscal tissues in patients undergoing arthroscopic partial meniscectomy for meniscal tear and to evaluate association with clinical outcomes. A total of 109 patients were recruited. Demographic and clinical data were collected. Visual Analogic Scale (VAS) measuring pain and Knee injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and at 2-years follow-up. Histological and immunohistochemical characterizations were performed on synovial membranes and meniscal tissues. More than half of the patients demonstrated synovial mononuclear cell infiltration and hyperplasia. Synovial fibrosis was present in most of the patients; marked vascularity and CD68 positivity were observed. Inflammation had an impact on both pain and knee symptoms. Patients with synovial inflammation had higher values of pre-operative VAS and inflammation. Higher pre-operative pain was observed in patients with meniscal MMP-13 production. In conclusion, multivariate analysis showed that synovial inflammation was associated with pre-operative total KOOS scores, knee symptoms, and pain. Moreover, meniscal MMP-13 expression was found to be associated with pre-operative pain in multivariate analysis. Thus, targeting inflammation of the synovial membrane and meniscus might reduce clinical symptoms and dysfunction at the time of surgery. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Graphical abstract

12 pages, 916 KiB

Open AccessArticle

Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1

by Tiina Lehtola, Elina Nummenmaa, Lauri Tuure, Mari Hämäläinen, Riina M. Nieminen, Teemu Moilanen, Antti Pemmari and Eeva Moilanen

Int. J. Mol. Sci. 2022, 23(7), 3880; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073880 - 31 Mar 2022

Cited by 4 | Viewed by 1810

Abstract

Mitogen-activated protein kinase phosphatase-1 (MKP-1) is upregulated in inflammation and reduces the activity of proinflammatory mitogen-activated protein kinases (MAP kinases) by dephosphorylation. MAP kinases are intracellular signaling pathways that mediate the cellular effects of proinflammatory cytokines. In the present study, we investigated the effects of the glucocorticoid dexamethasone on the expression of catabolic enzymes in chondrocytes and tested the hypothesis that these effects are mediated through MKP-1. Dexamethasone was found to significantly attenuate the expression of matrix metalloproteinase (MMP)-13 in human OA chondrocytes as well as in chondrocytes from MKP-1 WT mice, but not in chondrocytes from MKP-1 KO mice. Dexamethasone also increased the expression of MKP-1 in murine and human OA chondrocytes. Furthermore, p38 MAP kinase inhibitors significantly attenuated MMP-13 expression in human OA chondrocytes, while JNK MAP kinase inhibitors had no effect. The results indicate that the effect of dexamethasone on MMP-13 expression in chondrocytes was mediated by an MKP-1 and p38 MAP kinase-dependent manner. These findings, together with previous results, support the concept of MKP-1 as a protective factor in articular chondrocytes in inflammatory conditions and as a potential drug target to treat OA. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Figure 1

13 pages, 3524 KiB

Open AccessArticle

Shikonin Derivatives Inhibit Inflammation Processes and Modulate MAPK Signaling in Human Healthy and Osteoarthritis Chondrocytes

by Birgit Lohberger, Heike Kaltenegger, Nicole Eck, Dietmar Glänzer, Patrick Sadoghi, Andreas Leithner, Rudolf Bauer, Nadine Kretschmer and Bibiane Steinecker-Frohnwieser

Int. J. Mol. Sci. 2022, 23(6), 3396; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063396 - 21 Mar 2022

Cited by 5 | Viewed by 2136

Abstract

Osteoarthritis (OA) is the most common joint disorder and is characterized by the degeneration of articular cartilage. To develop new therapeutic approaches, we investigated the effect of shikonin derivatives on inflammation, MMP expression, and the regulation of MAPK signaling in human healthy (HC) and OA chondrocytes (pCH-OA). Viability was analyzed using the CellTiter-Glo^® Assay. Inflammatory processes were investigated using a proteome profiler™ assay. Furthermore, we analyzed the effects of the shikonin derivatives by protein expression analysis of the phosphorylation pattern and the corresponding downstream gene regulation using RT-qPCR. Both HC and pCH-OA showed a dose-dependent decrease in viability after treatment. The strongest effects were found for shikonin with IC₅₀ values of 1.2 ± 0.1 µM. Shikonin counteracts the inflammatory response by massively reducing the expression of the pro-inflammatory mediators. The phosphorylation level of ERK changed slightly. pJNK and pp38 showed a significant increase, and the downstream targets c/EBPs and MEF2c may play a role in the cartilage homeostasis. STAT3 phosphorylation decreased significantly and has a chondroprotective function through the regulation of cyclin D1 and Sox9. Our results demonstrate for the first time that shikonin derivatives have extensive effects on the inflammatory processes, MAPKs, and IL6/STAT3 downstream regulation in healthy and OA chondrocytes. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Figure 1

11 pages, 1024 KiB

Open AccessArticle

Modulation of miR-204 Expression during Chondrogenesis

by Luca Dalle Carbonare, Jessica Bertacco, Arianna Minoia, Mattia Cominacini, Lekhana Bhandary, Rossella Elia, Giovanni Gambaro, Monica Mottes and Maria Teresa Valenti

Int. J. Mol. Sci. 2022, 23(4), 2130; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042130 - 15 Feb 2022

Cited by 5 | Viewed by 1799

Abstract

RUNX2 and SOX9 are two pivotal transcriptional regulators of chondrogenesis. It has been demonstrated that RUNX2 and SOX9 physically interact; RUNX2 transactivation may be inhibited by SOX9. In addition, RUNX2 exerts reciprocal inhibition on SOX9 transactivity. Epigenetic control of gene expression plays a major role in the alternative differentiation fates of stem cells; in particular, it has been reported that SOX9 can promote the expression of miRNA (miR)-204. Our aim was therefore to investigate the miR-204-5p role during chondrogenesis and to identify the relationship between this miR and the transcription factors plus downstream genes involved in chondrogenic commitment and differentiation. To evaluate the role of miR-204 in chondrogenesis, we performed in vitro transfection experiments by using Mesenchymal Stem Cells (MSCs). We also evaluated miR-204-5p expression in zebrafish models (adults and larvae). By silencing miR-204 during the early differentiation phase, we observed the upregulation of SOX9 and chondrogenic related genes compared to controls. In addition, we observed the upregulation of COL1A1 (a RUNX2 downstream gene), whereas RUNX2 expression of RUNX2 was slightly affected compared to controls. However, RUNX2 protein levels increased in miR-204-silenced cells. The positive effects of miR204 silencing on osteogenic differentiation were also observed in the intermediate phase of osteogenic differentiation. On the contrary, chondrocytes’ maturation was considerably affected by miR-204 downregulation. In conclusion, our results suggest that miR-204 negatively regulates the osteochondrogenic commitment of MSCs, while it positively regulates chondrocytes’ maturation. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Figure 1

19 pages, 5268 KiB

Open AccessArticle

Novel NFκB Inhibitor SC75741 Mitigates Chondrocyte Degradation and Prevents Activated Fibroblast Transformation by Modulating miR-21/GDF-5/SOX5 Signaling

by Pei-Wei Weng, Vijesh Kumar Yadav, Narpati Wesa Pikatan, Iat-Hang Fong, I-Hsin Lin, Chi-Tai Yeh and Wei-Hwa Lee

Int. J. Mol. Sci. 2021, 22(20), 11082; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011082 - 14 Oct 2021

Cited by 7 | Viewed by 2813

Abstract

Osteoarthritis (OA) is a common articular disease manifested by the destruction of cartilage and compromised chondrogenesis in the aging population, with chronic inflammation of synovium, which drives OA progression. Importantly, the activated synovial fibroblast (AF) within the synovium facilitates OA through modulating key molecules, including regulatory microRNAs (miR’s). To understand OA associated pathways, in vitro co-culture system, and in vivo papain-induced OA model were applied for this study. The expression of key inflammatory markers both in tissue and blood plasma were examined by qRT-PCR, western blot, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assays. Herein, our result demonstrated, AF-activated human chondrocytes (AC) exhibit elevated NFκB, TNF-α, IL-6, and miR-21 expression as compared to healthy chondrocytes (HC). Importantly, AC induced the apoptosis of HC and inhibited the expression of chondrogenesis inducers, SOX5, TGF-β1, and GDF-5. NFκB is a key inflammatory transcription factor elevated in OA. Therefore, SC75741 (an NFκB inhibitor) therapeutic effect was explored. SC75741 inhibits inflammatory profile, protects AC-educated HC from apoptosis, and inhibits miR-21 expression, which results in the induced expression of GDF-5, SOX5, TGF-β1, BMPR2, and COL4A1. Moreover, ectopic miR-21 expression in fibroblast-like activated chondrocytes promoted osteoblast-mediated differentiation of osteoclasts in RW264.7 cells. Interestingly, in vivo study demonstrated SC75741 protective role, in controlling the destruction of the articular joint, through NFκB, TNF-α, IL-6, and miR-21 inhibition, and inducing GDF-5, SOX5, TGF-β1, BMPR2, and COL4A1 expression. Our study demonstrated the role of NFκB/miR-21 axis in OA progression, and SC75741’s therapeutic potential as a small-molecule inhibitor of miR-21/NFκB-driven OA progression. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Figure 1

Review

Jump to: Research

16 pages, 1087 KiB

Open AccessReview

Why Does Rehabilitation Not (Always) Work in Osteoarthritis? Does Rehabilitation Need Molecular Biology?

by Adam Zdziechowski, Anna Gluba-Sagr, Jacek Rysz and Marta Woldańska-Okońska

Int. J. Mol. Sci. 2023, 24(9), 8109; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24098109 - 30 Apr 2023

Cited by 1 | Viewed by 1508

Abstract

Osteoarthritis (OA) is a common disease among the human population worldwide. OA causes functional impairment, leads to disability and poses serious socioeconomic burden. The rehabilitation offers a function-oriented method to reduce the disability using diverse interventions (kinesiotherapy, physical therapy, occupational therapy, education, and pharmacotherapy). OA as a widespread disease among elderly patients is often treated by rehabilitation specialists and physiotherapists, however the results of rehabilitation are sometimes unsatisfactory. The understanding of molecular mechanisms activated by rehabilitation may enable the development of more effective rehabilitation procedures. Molecular biology methods may prove crucial in rehabilitation as the majority of rehabilitation procedures cannot be estimated in double-blinded placebo-controlled trials commonly used in pharmacotherapy. This article attempts to present and estimate the role of molecular biology in the development of modern rehabilitation. The role of clinicians in adequate molecular biology experimental design is also described. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Figure 1

13 pages, 1111 KiB

Open AccessReview

Oral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review

by Marcin Derwich, Bartłomiej Górski, Elie Amm and Elżbieta Pawłowska

Int. J. Mol. Sci. 2023, 24(5), 4925; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054925 - 03 Mar 2023

Cited by 5 | Viewed by 4449

Abstract

Temporomandibular disorders (TMDs) occur frequently within the general population and are the most common non-dental cause of orofacial pain. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease (DJD). There have been several different methods of treatment of TMJ OA listed, including pharmacotherapy among others. Due to its anti-aging, antioxidative, bacteriostatic, anti-inflammatory, immuno-stimulating, pro-anabolic and anti-catabolic properties, oral glucosamine seems to be a potentially very effective agent in the treatment of TMJ OA. The aim of this review was to critically assess the efficacy of oral glucosamine in the treatment of TMJ OA on the basis of the literature. PubMed and Scopus databases were analyzed with the keywords: (temporomandibular joints) AND ((disorders) OR (osteoarthritis)) AND (treatment) AND (glucosamine). After the screening of 50 results, eight studies have been included in this review. Oral glucosamine is one of the symptomatic slow-acting drugs for osteoarthritis. There is not enough scientific evidence to unambiguously confirm the clinical effectiveness of glucosamine supplements in the treatment of TMJ OA on the basis of the literature. The most important aspect affecting the clinical efficacy of oral glucosamine in the treatment of TMJ OA was the total administration time. Administration of oral glucosamine for a longer period of time, i.e., 3 months, led to a significant reduction in TMJ pain and a significant increase in maximum mouth opening. It also resulted in long-term anti-inflammatory effects within the TMJs. Further long-term, randomized, double-blind studies, with a unified methodology, ought to be performed to draw the general recommendations for the use of oral glucosamine in the treatment of TMJ OA. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures

Figure 1

21 pages, 979 KiB

Open AccessReview

by Maria Peshkova, Alexey Lychagin, Marina Lipina, Berardo Di Matteo, Giuseppe Anzillotti, Flavio Ronzoni, Nastasia Kosheleva, Anastasia Shpichka, Valeriy Royuk, Victor Fomin, Eugene Kalinsky, Peter Timashev and Elizaveta Kon

Int. J. Mol. Sci. 2022, 23(5), 2767; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052767 - 02 Mar 2022

Cited by 37 | Viewed by 5647

Abstract

Osteoarthritis (OA) is a common degenerative joint disease treated mostly symptomatically before approaching its definitive treatment, joint arthroplasty. The rapidly growing prevalence of OA highlights the urgent need for a more efficient treatment strategy and boosts research into the mechanisms of OA incidence and progression. As a multifactorial disease, many aspects have been investigated as contributors to OA onset and progression. Differences in gender appear to play a role in the natural history of the disease, since female sex is known to increase the susceptibility to its development. The aim of the present review is to investigate the cues associated with gender by analyzing various hormonal, anatomical, molecular, and biomechanical parameters, as well as their differences between sexes. Our findings reveal the possible implications of gender in OA onset and progression and provide evidence for gaps in the current state of art, thus suggesting future research directions. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

18 pages, 878 KiB

Open AccessReview

Oxygen-Ozone Therapy for Reducing Pro-Inflammatory Cytokines Serum Levels in Musculoskeletal and Temporomandibular Disorders: A Comprehensive Review

by Alessandro de Sire, Nicola Marotta, Martina Ferrillo, Francesco Agostini, Cristiano Sconza, Lorenzo Lippi, Stefano Respizzi, Amerigo Giudice, Marco Invernizzi and Antonio Ammendolia

Int. J. Mol. Sci. 2022, 23(5), 2528; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052528 - 25 Feb 2022

Cited by 51 | Viewed by 6992

Abstract

To date, the application of oxygen-ozone (O₂O₃) therapy has significantly increased in the common clinical practice in several pathological conditions. However, beyond the favorable clinical effects, the biochemical effects of O₂O₃ are still far from being understood. This comprehensive review aimed at investigating the state of the art about the effects of O₂O₃ therapy on pro-inflammatory cytokines serum levels as a modulator of oxidative stress in patients with musculoskeletal and temporomandibular disorders (TMD). The efficacy of O₂O₃ therapy could be related to the moderate oxidative stress modulation produced by the interaction of ozone with biological components. More in detail, O₂O₃ therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune overactivation. In this context, most musculoskeletal and temporomandibular disorders (TMD) share these two pathophysiological processes. Despite the paucity of in vivo studies, this comprehensive review suggests that O₂O₃ therapy might reduce serum levels of interleukin 6 in patients with TMD, low back pain, knee osteoarthritis and rheumatic diseases with a concrete and measurable interaction with the inflammatory pathway. However, to date, further studies are needed to clarify the effects of this promising therapy on inflammatory mediators and their clinical implications. Full article

(This article belongs to the Special Issue Osteoarthritis 2.0: From Molecular Pathways to Therapeutic Advances)

► Show Figures