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Advances in the Molecular Mechanisms of Inflammatory Arthritis and Inflammation-Related...
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Advances in the Molecular Mechanisms of Inflammatory Arthritis and Inflammation-Related Bone Changes

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (1 May 2025) | Viewed by 6921

Special Issue Editors

Prof. Dr. Michael Schirmer

E-Mail Website
Guest Editor
Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria
Interests: rheumatische polymyalgie; Rheumatology; arthritis; giant cell arteritis
Special Issues, Collections and Topics in MDPI journals
Dr. Carlo Perricone

E-Mail Website
Co-Guest Editor
Rheumatology, Department of Medicine and Surgery, University of Perugia, p.le Menghini 1, 06129 Perugia, Italy
Interests: systemic lupus erythematosus; antiphospholipid syndrome; rheumatoid arthritis; genetic of autoimmune diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue aims to summarise advances in the molecular mechanisms of inflammatory processes leading to arthritis and bone changes, and thus focuses on both the immunological and the osteological organ system. Advances in autoimmunity and auto-inflammation as well as advances in our knowledge of bone loss and bone growth are welcome for this Special Issue. In addition, osteo-immunological aspects describing the interactions between the immunological and the osteological systems are encouraged, as are studies on the intracellular, cellular and in vivo levels. The knowledge about such molecular mechanisms will provide new stimuli for further clinical research, including new treatment options for inflammatory arthritis in the acute and the chronic disease-phases and immune-related problems after prosthetic or other bone surgery.

Prof. Dr. Michael Schirmer
Dr. Carlo Perricone
Guest Editors

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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • inflammatory arthritis
  • molecular mechanisms
  • bone changes
  • osteoimmunology
  • autoimmunity

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Published Papers (3 papers)

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Research

14 pages, 2213 KiB  
Article
Reduced Bone Quality of Sacrum and Lumbal Vertebrae Spongiosa in Toll-like Receptor 2- and Toll-like Receptor 4-Knockout Mice: A Blinded Micro-Computerized Analysis
by Kilian Roth, Johannes Dominikus Pallua, Gerald Degenhart, Tobias De Zordo, Christian Kremser, Christian Reif, Werner Streif and Michael Schirmer
Biomolecules 2025, 15(2), 239; https://doi.org/10.3390/biom15020239 - 7 Feb 2025
Viewed by 1269
Abstract
Toll-like receptors (TLRs) are pivotal in modulating immune responses and have been implicated in bone remodeling. This in vivo study investigates the impact of TLR2 and TLR4 signaling on trabecular bone structure using micro-computed tomography in a murine model. Sacrum and lumbar vertebrae [...] Read more.
Toll-like receptors (TLRs) are pivotal in modulating immune responses and have been implicated in bone remodeling. This in vivo study investigates the impact of TLR2 and TLR4 signaling on trabecular bone structure using micro-computed tomography in a murine model. Sacrum and lumbar vertebrae (L5, L6) from wildtype (WT), TLR2-knockout (TLR2-KO), and TLR4-knockout (TLR4-KO) mice were analyzed, with trabecular parameters such as connectivity density (Conn-Dens), trabecular thickness (DT-TbTh), and variability metrics (DT-Tb,(1/N),SD and DT-TbThSD) assessed. The results revealed significant differences among genotypes: TLR4-KO mice exhibited increased variability in trabecular distribution, indicating less stable bone structures, while TLR-KO mice showed lower variability in trabecular thickness, suggesting enhanced uniformity and robustness. BV/TV and 3D reconstructions highlighted lower bone volume fractions in the sacrum compared to lumbar vertebrae across genotypes, consistent with human observations of reduced sacral bone volume in spondyloarthritis (SpA). Interestingly, bone changes were independent of immunization-induced SpA, emphasizing a direct role in TLR signaling. These findings provide novel insights into the role of TLRs in bone microarchitecture and suggest implications for bone-related pathologies, particularly those involving inflammatory pathways. Future research may explore the translational relevance of TLR-mediated mechanisms in osteopenia and osteoporosis. Full article
(This article belongs to the Special Issue Advances in the Molecular Mechanisms of Inflammatory Arthritis and Inflammation-Related Bone Changes)
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16 pages, 2618 KiB  
Article
Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors
by Daniel Sobral, Ana Filipa Fernandes, Miguel Bernardes, Patrícia Pinto, Helena Santos, João Lagoas-Gomes, José Tavares-Costa, José A. P. Silva, João Madruga Dias, Alexandra Bernardo, Jean-Charles Gaillard, Jean Armengaud, Vladimir Benes, Lúcia Domingues, Sara Maia, Jaime C. Branco, Ana Varela Coelho and Fernando M. Pimentel-Santos
Biomolecules 2024, 14(3), 382; https://doi.org/10.3390/biom14030382 - 21 Mar 2024
Viewed by 2530
Abstract
This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = [...] Read more.
This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered. Full article
(This article belongs to the Special Issue Advances in the Molecular Mechanisms of Inflammatory Arthritis and Inflammation-Related Bone Changes)
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12 pages, 781 KiB  
Article
Pro-Inflammatory Biomarkers Combined with Body Composition Display a Strong Association with Knee Osteoarthritis in a Community-Based Study
by Nader Tarabeih, Alexander Kalinkovich, Adel Shalata, Orabi Higla and Gregory Livshits
Biomolecules 2023, 13(9), 1315; https://doi.org/10.3390/biom13091315 - 28 Aug 2023
Cited by 6 | Viewed by 2327
Abstract
Knee osteoarthritis (KOA) is one of the most common progressive, age-dependent chronic degenerative joint diseases. KOA often develops as a result of a gradual articular cartilage loss caused by its wear and tear. Numerous studies suggest that the degradation of the knee joint [...] Read more.
Knee osteoarthritis (KOA) is one of the most common progressive, age-dependent chronic degenerative joint diseases. KOA often develops as a result of a gradual articular cartilage loss caused by its wear and tear. Numerous studies suggest that the degradation of the knee joint involves inflammatory components. This process is also associated with body composition, particularly being overweight and muscle mass loss. The present study aimed to search for novel circulating KOA inflammatory biomarkers, taking into account body composition characteristics. To this aim, we recruited 98 patients diagnosed and radiologically confirmed with KOA and 519 healthy controls from the Arab community in Israel. A panel of soluble molecules, related to inflammatory, metabolic, and musculoskeletal disorders, was measured by ELISA in plasma samples, while several body composition parameters were assessed with bioimpedance analysis. Statistical analysis, including multivariable logistic regression, revealed a number of the factors significantly associated with KOA, independently of age and sex. The most significant independent associations [OR (95% CI)] were fat body mass/body weight index—1.56 (1.20–2.02), systemic immune-inflammation index—4.03 (2.23–7.27), circulating vaspin levels—1.39 (1.15–1.68), follistatin/FSTL1 ratio—1.32 (1.02–1.70), and activin A/FSTL1 ratio—1.33 (1.01–1.75). Further clinical studies are warranted to confirm the relevance of these KOA-associated biological factors. Hereafter, they could serve as reliable biomarkers for KOA in the general human population. Full article
(This article belongs to the Special Issue Advances in the Molecular Mechanisms of Inflammatory Arthritis and Inflammation-Related Bone Changes)
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