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Arthritis: From Molecular Basis to Therapy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 October 2026 | Viewed by 3800

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Editor

Dr. Cinzia Rotondo

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Guest Editor

Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
Interests: therapeutic implication; systemic sclerosi

Special Issue Information

Dear Colleagues,

In recent decades, our knowledge of the pathogenic processes behind arthritis has significantly revolutionised the therapeutic landscape, so much so that the main scientific societies have started to talk about “precision medicine” and “tailored therapy”. However, despite considerable progress, many needs remain unmet, such the management of the pre-clinical phase of rheumatoid arthritis, the possible use of dual biologic treatment, the overall definition of disease activity in arthritis with multiple domains, the influence of b/ts-DMARDs on comorbidities, new pathogenetic pathways, innovative molecular targets, biomarkers and predictors, and treatment responses.

This Special Issue of IJMS, entitled ‘Arthritis: From Molecular Basis to Therapy’, is led by Dr. Cinzia Rotondo and is designed to collect as much data as possible on new insights, recent developments and discoveries in pathogenetic pathways, current challenges, real-world evidence, and future treatment perspectives in the field of arthritis.

Dr. Cinzia Rotondo
Guest Editor

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Keywords

comorbidities
biomarkers
inflammation
autoimmune disease
systemic disease
arthritis
autoimmune disease
psoriasis
axial involvement
biological drugs
target synthetic DMARDs
pathogenesis
rheumatoid arthritis
spondyloarthritis
psoriatic arthritis

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Published Papers (4 papers)

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Research

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22 pages, 11640 KB

Open AccessArticle

Dissociation Between Functional Performance and Structural Joint Damage Following Sertraline Treatment in Collagen-Induced Arthritis

by Grzegorz Chmielewski, Mateusz Mikiewicz, Jakub Kuna, Łukasz Jaśkiewicz, Joanna Czerwińska, Michał Majewski and Magdalena Krajewska-Włodarczyk

Int. J. Mol. Sci. 2026, 27(16), 7251; https://doi.org/10.3390/ijms27167251 - 14 Aug 2026

Cited by 1 | Viewed by 163

Abstract

Rheumatoid arthritis is a chronic inflammatory joint disease often accompanied by depressive symptoms, in which functional impairment does not always reflect the extent of structural joint damage. Sertraline, a selective serotonin reuptake inhibitor, may influence behavioural and neuroimmune pathways, but its effects on the relationship between joint pathology and functional performance remain unclear. This study evaluated whether sertraline affects functional performance independently of histopathological joint damage in collagen-induced arthritis. Male Wistar rats with collagen-induced arthritis were assigned to untreated or treatment groups receiving sertraline, methotrexate, combined methotrexate and sertraline, infliximab, or tocilizumab. Functional performance was assessed by spontaneous wheel-running activity, body weight, and joint swelling. At week 12, ankle joints underwent histopathological evaluation, and haematological parameters and serum cytokines were analysed. Sertraline did not reduce synovial inflammation, cartilage damage, or bone erosion, although sertraline-treated rats showed a smaller numerical decline in spontaneous wheel-running activity than rats with untreated collagen-induced arthritis. In contrast, methotrexate and biologic therapies improved both structural damage and functional outcomes. Functional performance did not consistently correlate with histopathological severity or circulating cytokine levels. Sertraline did not produce a significant improvement in histopathological outcomes compared with untreated collagen-induced arthritis, while the smaller numerical decline in exploratory wheel-running activity should be interpreted cautiously. Full article

(This article belongs to the Special Issue Arthritis: From Molecular Basis to Therapy)

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18 pages, 9574 KB

Open AccessArticle

Chondroprotective Effects of Enzyme-Treated Extract from Cervus elaphus L. in a Rat Model of Osteoarthritis

by Min Ju Kim, Hyeon-Ji Lim, In-Sun Park, Bongsuk Choi, Taehee Kim, HyoungKwon Cho, Seon-Young Kim and Chan-Hun Jung

Int. J. Mol. Sci. 2026, 27(13), 5785; https://doi.org/10.3390/ijms27135785 - 26 Jun 2026

Viewed by 328

Abstract

Osteoarthritis (OA) is a chronic, debilitating degenerative joint disease whose prevalence is rising markedly with the rapid aging of the global population. In this study, we investigated the chondroprotective efficacy of NP-2007, an enzymatically hydrolyzed low-molecular-weight collagen from Cervi cornu, using IL-1β-stimulated SW1353 human chondrocyte cells and a medial meniscal transection (MMT)-induced OA rat model. In SW1353 cells, NP-2007 considerably suppressed the expression of inflammatory mediators (iNOS, COX-2) and cytokines (TNF-α, IL-6) without cytotoxicity. Crucially, it restored matrix homeostasis by downregulating catabolic enzymes (MMP-3, MMP-13, and ADAMTS-5) and upregulating anabolic markers (COL2A1, aggrecan), a process associated with the modulation of the Wnt/β-catenin and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways and the recovery of the master chondrogenic factor SOX9. These in vitro findings were consistent with the in vivo results from the MMT model, where oral administration of NP-2007 (50 and 200 mg/kg) for 8 weeks effectively preserved articular cartilage structure and proteoglycan content while markedly reducing serum levels of catabolic biomarkers, including MMP-13 and COMP. Collectively, our findings demonstrate that NP-2007 exerts potent chondroprotective effects by modulating the balance between cartilage degradation and synthesis, suggesting its potential as a therapeutic candidate for the management of OA. Full article

(This article belongs to the Special Issue Arthritis: From Molecular Basis to Therapy)

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13 pages, 332 KB

Open AccessArticle

HLA-B*51 Beyond Behcet’s Disease: Topography of Symptoms, Associated Diagnoses, and Characterization of Chronic Inflammatory Arthritis Phenotypes

by Cinzia Rotondo, Giuseppe Busto, Raffaele Barile, Giulio Giancaspro, Brunella Capuano, Valeria Rella, Francesco Paolo Cantatore and Addolorata Corrado

Int. J. Mol. Sci. 2026, 27(9), 3721; https://doi.org/10.3390/ijms27093721 - 22 Apr 2026

Cited by 1 | Viewed by 1143

Abstract

In the clinical context of the new medical concept of diseases related to the Major Histocompatibility Complex class I (MHC-I-opathy), contrasting data are available on the possible association among HLA-B*51, Behcet’s disease (BD), and spondyloarthritis (SpA). The aim of this retrospective study on a cohort of HLA-B*51-positive patients who were clinically observed for almost 5 years is primarily to evaluate which classification criteria they satisfy among BD, axial (ax) or peripheral (p) SpA, and psoriatic arthritis (PsA). Furthermore, we characterized the possible impact of different arthritis phenotypes on the most frequent extra-articular clinical manifestations in BD, ax-SpA, p-SpA, and PsA. A comparison with HLA-B*51-negative patients (matched with HLA-B*51-positive patients for age, gender, and diagnosis, by mean propensity score) was also performed to evaluate the true impact on clinical manifestations of HLA-B*51. We conducted a monocentric retrospective study from 2013 to 2025. The inclusion criteria were HLA-B*51 positivity, the availability of the entire MHC-I class test, and rheumatological clinical follow-up of at least 5 years. The exclusion criterion was positivity for clinically important MCH-I loci other than HLA-B*51. A total of 105 patients met the inclusion criteria in an average clinical observation period of 8.4 ± 2.9 years. All patients were Apulian and were HLA-B* 51 positive. During the follow-up, 32 patients (31%) met the BD criteria, 17 (16%) met the PsA criteria, 25 (24%) met the p-SpA criteria, and 13 (12%) met the ax-SpA criteria. Of note, 16% and 34% of BD patients met the ax-SpA and p-SpA ASAS criteria, respectively. Prevalent articular phenotypes in this HLA-B*51 cluster of patients are a polyarticular pattern and enthesis involvement in all disease groups. In BD patients, axial involvement was associated with a significantly higher percentage of neurological manifestations (40% vs. 7%, p = 0.043) and inflammatory bowel disease (IBD) (100% vs. 15%, p = 0.0001), compared to patients with exclusive peripheral joint involvement. This latest data on IBD remains significant, even in comparison with HLA-B*51 negative patients (33%; p = 0.035). In the p-SpA group, a significantly higher rate of uveitis (28%) was observed compared to both ax-SpA with HLA-B*51-positive (0%, p = 0.035) and p-SpA with HLA-B*51-negative patients (4%, p = 0.030). A high percentage of multi-drug failures was highlighted in patients with PsA (60%) and p-SpA (40%). This study provides new data on the association between HLA-B*51 and the onset of BD and/or SpA or PsA, and its possible impact on extra-articular manifestations. We confirm the higher prevalence of the peripheral articular phenotype in BD, but we also highlight a specific association between the rarer axial involvement and gastrointestinal involvement in HLA-B*51 patients. In SpA, the peripheral articular phenotype appears to be associated with a higher occurrence of uveitis in the presence of HLA-B*51. Full article

(This article belongs to the Special Issue Arthritis: From Molecular Basis to Therapy)

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Review

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26 pages, 379 KB

Open AccessReview

Current State of Orthobiologics in Treatment of Knee Osteoarthritis—Future Directions

by Woojin Lee, Qing Zhao Ruan, Jamal J. Hasoon, Ronald J. Kulich, Timothy R. Deer, Dawood Sayed, Franzes Anne Z. Liongson, Elizabeth Hatfield, Maged Guirguis, Alan D. Kaye, Zachary L. McCormick, Robert Jason Yong and Christopher L. Robinson

Int. J. Mol. Sci. 2026, 27(11), 4738; https://doi.org/10.3390/ijms27114738 - 25 May 2026

Cited by 1 | Viewed by 1735

Abstract

As the population ages, the incidence and prevalence of musculoskeletal degeneration, such as osteoarthritis, increase. While the currently accepted treatment options provide symptomatic and functional improvement, they do not halt the progression of osteoarthritis. This results in the eventual need for surgery for many patients with advanced osteoarthritis. Due to the seemingly inevitable progression of OA, many clinicians and researchers have shifted their focus to regenerative therapies. Orthobiologics, a specific type of regenerative therapy designed to treat orthopedic conditions, has been gaining traction in recent years due to the utilization of autologous biological substances and synthetic peptides in healing musculoskeletal injuries and degenerative conditions. Orthobiologics can be distinguished into one of four classes: cell-based, biologic fluids-based, matrix-based, molecular-based, and based on their composition. In this review, key examples of each class, mechanism of action, and current clinical data for each agent are examined. Limitations of current orthobiologics involve a lack of standardization in the preparation and administration of each agent, as well as uniformity in assessment endpoints across different clinical studies. Lastly, we will discuss future directions of orthobiologics as a therapy for the treatment of osteoarthritis. Full article

(This article belongs to the Special Issue Arthritis: From Molecular Basis to Therapy)

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