International Journal of Molecular Sciences

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17 pages, 601 KiB

Open AccessArticle

Disease Activity-Dependent Siglec-1 Expression on Monocyte Subsets of Patients with Idiopathic Inflammatory Myopathies

by Sándor Baráth, Melinda Nagy-Vincze, Zsuzsanna Kun, Dorottya Szinay, Zoltán Griger, Jr., Tibor Gábor Béldi, Katalin Szabó, Marianna Száraz-Széles, Zsuzsanna Hevessy and Zoltán Griger

Int. J. Mol. Sci. 2025, 26(10), 4950; https://doi.org/10.3390/ijms26104950 - 21 May 2025

Abstract

Interferon signature is one of the key pathogenic pathways in idiopathic inflammatory myopathies (IIMs), particularly in dermatomyositis (DM). The aim of this study was to analyze Siglec-1, an interferon-inducible receptor, on different monocyte subsets in IIM subtypes and investigate its association with disease [...] Read more.

Interferon signature is one of the key pathogenic pathways in idiopathic inflammatory myopathies (IIMs), particularly in dermatomyositis (DM). The aim of this study was to analyze Siglec-1, an interferon-inducible receptor, on different monocyte subsets in IIM subtypes and investigate its association with disease activity measures. Siglec-1 expression was measured by 8-color flow cytometry in 62 IIM patients and 10 healthy controls (HC). Disease activity was assessed using the International Myositis Assessment and Clinical Studies (IMACS) core set measures. Active DM patients exhibited significantly higher Siglec-1 mean fluorescence intensity (MFI) compared to inactive subgroups and HCs in every monocyte subset. Intermediate monocytes displayed the highest Siglec-1 expression across all groups and the strongest associations between disease activity markers. Siglec-1 expression on monocyte subsets was strongly associated with global, extramuscular global, constitutional, cutaneous, muscular, and gastrointestinal activity measures, but not with pulmonary, skeletal, and cardiac activities in the DM population. The best indicator of DM global disease activity among the examined biomarkers was Siglec-1 MFI on intermediate monocytes. Siglec-1 on intermediate monocytes correlates strongly with organ-specific clinical and biochemical markers of disease activity; therefore, it is a candidate biomarker for monitoring IIM disease activity. Siglec-1 could be useful in patient selection for interferon-targeted treatments. Full article

(This article belongs to the Special Issue Highlights in Pathophysiology of the Musculoskeletal System, 2nd Edition)

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8 pages, 696 KiB

Open AccessArticle

Effect of Single Session of Swedish Massage on Circulating Levels of Interleukin-6 and Insulin-like Growth Factor 1

by Ville Stenbäck, Inka Lehtonen, Kari Antero Mäkelä, Ghulam Shere Raza, Venla Ylinen, Rasmus Valtonen, Tuomas Hamari, Jaroslaw Walkowiak, Mikko Tulppo and Karl-Heinz Herzig

Int. J. Mol. Sci. 2024, 25(17), 9135; https://doi.org/10.3390/ijms25179135 - 23 Aug 2024

Cited by 3 | Viewed by 2583

Abstract

Massage therapy increases muscle blood flow and heat, relieving pain, improving immune function, and increasing vagal activity. The mechanisms are unclear. Muscles release cytokines and other peptides called myokines. These myokines exert their effects on different tissues and organs in para-, auto-, and [...] Read more.

Massage therapy increases muscle blood flow and heat, relieving pain, improving immune function, and increasing vagal activity. The mechanisms are unclear. Muscles release cytokines and other peptides called myokines. These myokines exert their effects on different tissues and organs in para-, auto-, and endocrine fashion. The aim of this intervention study was to investigate if massage therapy affects circulating myokine levels. A total of 46 healthy, normal-weight subjects (15 men) aged 18–35 were recruited. Forty-five minutes of massage Swedish therapy was applied to the back and hamstrings. Blood samples via cannula were taken at the baseline, during the massage (30 min), end of the massage (45 min), and 30 min and 1 h after the massage. Interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) were measured as surrogate markers by ELISAs. There was a significant increase in IL-6 from 1.09 pg/mL to 1.85 pg/mL over time (Wilks’ Lambda Value 0.545, p < 0.000; repeated measures ANOVA). Pair-wise comparisons showed a significant increase after 1 h of massage. No significant increase was observed in IGF-1 levels. The change in myokine levels was not correlated with muscle mass (p = 0.16, 0.74). The increase in IL-6 suggests that there might be anti-inflammatory effects, affecting glucose and lipid metabolism pathways via IL-6 signaling to muscles, fat tissue, and the liver. Full article

(This article belongs to the Special Issue Highlights in Pathophysiology of the Musculoskeletal System, 2nd Edition)

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24 pages, 5969 KiB

Open AccessArticle

Pathophysiological Aspects of Muscle Atrophy and Osteopenia Induced by Chronic Constriction Injury (CCI) of the Sciatic Nerve in Rats

by Francesca Bosco, Lorenza Guarnieri, Saverio Nucera, Miriam Scicchitano, Stefano Ruga, Antonio Cardamone, Samantha Maurotti, Cristina Russo, Anna Rita Coppoletta, Roberta Macrì, Irene Bava, Federica Scarano, Fabio Castagna, Maria Serra, Rosamaria Caminiti, Jessica Maiuolo, Francesca Oppedisano, Sara Ilari, Filomena Lauro, Luigi Giancotti, Carolina Muscoli, Cristina Carresi, Ernesto Palma, Micaela Gliozzi, Vincenzo Musolino and Vincenzo Mollace Show full author list Hide full author list

Int. J. Mol. Sci. 2023, 24(4), 3765; https://doi.org/10.3390/ijms24043765 - 13 Feb 2023

Cited by 9 | Viewed by 3250

Abstract

Skeletal muscle atrophy is a condition characterized by a loss of muscle mass and muscle strength caused by an imbalance between protein synthesis and protein degradation. Muscle atrophy is often associated with a loss of bone mass manifesting as osteoporosis. The aim of [...] Read more.

Skeletal muscle atrophy is a condition characterized by a loss of muscle mass and muscle strength caused by an imbalance between protein synthesis and protein degradation. Muscle atrophy is often associated with a loss of bone mass manifesting as osteoporosis. The aim of this study was to evaluate if chronic constriction injury (CCI) of the sciatic nerve in rats can be a valid model to study muscle atrophy and consequent osteoporosis. Body weight and body composition were assessed weekly. Magnetic resonance imaging (MRI) was performed on day zero before ligation and day 28 before sacrifice. Catabolic markers were assessed via Western blot and Quantitative Real-time PCR. After the sacrifice, a morphological analysis of the gastrocnemius muscle and Micro-Computed Tomography (Micro-CT) on the tibia bone were performed. Rats that underwent CCI had a lower body weight increase on day 28 compared to the naive group of rats (p < 0.001). Increases in lean body mass and fat mass were also significantly lower in the CCI group (p < 0.001). The weight of skeletal muscles was found to be significantly lower in the ipsilateral hindlimb compared to that of contralateral muscles; furthermore, the cross-sectional area of muscle fibers decreased significantly in the ipsilateral gastrocnemius. The CCI of the sciatic nerve induced a statistically significant increase in autophagic and UPS (Ubiquitin Proteasome System) markers and a statistically significant increase in Pax-7 (Paired Box-7) expression. Micro-CT showed a statistically significant decrease in the bone parameters of the ipsilateral tibial bone. Chronic nerve constriction appeared to be a valid model for inducing the condition of muscle atrophy, also causing changes in bone microstructure and leading to osteoporosis. Therefore, sciatic nerve constriction could be a valid approach to study muscle–bone crosstalk and to identify new strategies to prevent osteosarcopenia. Full article

(This article belongs to the Special Issue Highlights in Pathophysiology of the Musculoskeletal System, 2nd Edition)

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Review

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26 pages, 564 KiB

Open AccessReview

RNA Modifications in Osteoarthritis: Epitranscriptomic Insights into Pathogenesis and Therapeutic Targets

by Shabnam Radbakhsh, Mehdi Najar, Makram Merimi, Mohamed Benderdour, Julio C. Fernandes, Johanne Martel-Pelletier, Jean-Pierre Pelletier and Hassan Fahmi

Int. J. Mol. Sci. 2025, 26(10), 4955; https://doi.org/10.3390/ijms26104955 - 21 May 2025

Abstract

Osteoarthritis (OA) is a chronic joint disorder characterized by progressive degeneration of articular cartilage, pain, synovial inflammation, and bone remodeling. Post-transcriptional RNA modifications, known as epitranscriptome, are a group of biochemical alterations in the primary RNA transcript that might influence RNA structure, stability, [...] Read more.

Osteoarthritis (OA) is a chronic joint disorder characterized by progressive degeneration of articular cartilage, pain, synovial inflammation, and bone remodeling. Post-transcriptional RNA modifications, known as epitranscriptome, are a group of biochemical alterations in the primary RNA transcript that might influence RNA structure, stability, and function. Different kinds of RNA modifications have been recognized, such as methylation, acetylation, pseudouridylation, and phosphorylation. N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), 2′-O-ribose methylation (2′-O-Me), and pseudouridylation (Ψ) are the most prevalent RNA modifications. Recent studies have shown that disruption in these modifications can interfere with gene expression and protein function. Here, we will review all types of RNA modifications and how they contribute to the onset and progression of OA. To the best of our knowledge, this is the first review comprehensively addressing all epitranscriptomic modifications in OA. Full article

(This article belongs to the Special Issue Highlights in Pathophysiology of the Musculoskeletal System, 2nd Edition)

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13 pages, 593 KiB

Open AccessReview

Current Methods in Synovial Fluid Microbiota Characterization: A Systematic Review

by Elena Bardi, Daniele D’Arrigo, Chiara Pozzi, Andrea Gatti, Luca Bertolino, Alberto Favaro, Maria Rescigno and Tommaso Bonanzinga

Int. J. Mol. Sci. 2025, 26(10), 4690; https://doi.org/10.3390/ijms26104690 - 14 May 2025

Viewed by 105

Abstract

Evidence suggests that a cross-talk between the gut microbiota and joint health exists in a paradigm known as the gut–joint axis. Recent studies have also reported the presence of microorganisms potentially involved in the pathogenesis and progression of arthritis in synovial joints, previously [...] Read more.

Evidence suggests that a cross-talk between the gut microbiota and joint health exists in a paradigm known as the gut–joint axis. Recent studies have also reported the presence of microorganisms potentially involved in the pathogenesis and progression of arthritis in synovial joints, previously believed to be sterile. This systematic review describes in detail the methodologies employed to characterize the microbiota in human synovial fluid (SF). A literature search was conducted in PubMed, Embase, and Web of Science up to 5 February 2025. Nine studies aimed to characterize the SF microbiome using next-generation sequencing or polymerase chain reaction. Eight studies detected bacterial DNA in SF. However, significant heterogeneity and incomplete reporting in methodologies, including sample collection and preparation, contamination management, DNA extraction and amplification, sequencing technology, targeted 16S rRNA or ITS regions, and bioinformatics processing, limit the comparability and significance of findings. Given the potential implications for understanding arthritis mechanisms and developing targeted treatments, a standardized methodological and reporting approach in SF microbiota characterization is needed to enhance the reproducibility and the relevance of results. Full article

(This article belongs to the Special Issue Highlights in Pathophysiology of the Musculoskeletal System, 2nd Edition)

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16 pages, 410 KiB

Open AccessReview

Towards Precision in Sarcopenia Assessment: The Challenges of Multimodal Data Analysis in the Era of AI

by Valerio Caputo, Ivan Letteri, Silvano Junior Santini, Gaia Sinatti and Clara Balsano

Int. J. Mol. Sci. 2025, 26(9), 4428; https://doi.org/10.3390/ijms26094428 - 7 May 2025

Viewed by 160

Abstract

Sarcopenia, a condition characterised by the progressive decline in skeletal muscle mass and function, presents significant challenges in geriatric healthcare. Despite advances in its management, complex etiopathogenesis and the heterogeneity of diagnostic criteria underlie the limited precision of existing assessment methods. Therefore, efforts [...] Read more.

Sarcopenia, a condition characterised by the progressive decline in skeletal muscle mass and function, presents significant challenges in geriatric healthcare. Despite advances in its management, complex etiopathogenesis and the heterogeneity of diagnostic criteria underlie the limited precision of existing assessment methods. Therefore, efforts are needed to improve the knowledge and pave the way for more effective management and a more precise diagnosis. To this purpose, emerging technologies such as artificial intelligence (AI) can facilitate the identification of novel and accurate biomarkers by modelling complex data resulting from high-throughput technologies, fostering the setting up of a more precise approach. Based on such considerations, this review explores AI’s transformative potential, illustrating studies that integrate AI, especially machine learning and deep learning, with heterogeneous data such as clinical, anthropometric and molecular data. Overall, the present review will highlight the relevance of large-scale, standardised studies to validate biomarker signatures using AI-driven approaches. Full article

(This article belongs to the Special Issue Highlights in Pathophysiology of the Musculoskeletal System, 2nd Edition)

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26 pages, 5175 KiB

Open AccessReview

Emerging Therapeutic Strategies in Sarcopenia: An Updated Review on Pathogenesis and Treatment Advances

by Alfred Najm, Adelina-Gabriela Niculescu, Alexandru Mihai Grumezescu and Mircea Beuran

Int. J. Mol. Sci. 2024, 25(8), 4300; https://doi.org/10.3390/ijms25084300 - 12 Apr 2024

Cited by 15 | Viewed by 10654

Abstract

Sarcopenia is a prevalent degenerative skeletal muscle condition in the elderly population, posing a tremendous burden on diseased individuals and healthcare systems worldwide. Conventionally, sarcopenia is currently managed through nutritional interventions, physical therapy, and lifestyle modification, with no pharmaceutical agents being approved for [...] Read more.

Sarcopenia is a prevalent degenerative skeletal muscle condition in the elderly population, posing a tremendous burden on diseased individuals and healthcare systems worldwide. Conventionally, sarcopenia is currently managed through nutritional interventions, physical therapy, and lifestyle modification, with no pharmaceutical agents being approved for specific use in this disease. As the pathogenesis of sarcopenia is still poorly understood and there is no treatment recognized as universally effective, recent research efforts have been directed at better comprehending this illness and diversifying treatment strategies. In this respect, this paper overviews the new advances in sarcopenia treatment in correlation with its underlying mechanisms. Specifically, this review creates an updated framework for sarcopenia, describing its etiology, pathogenesis, risk factors, and conventional treatments, further discussing emerging therapeutic approaches like new drug formulations, drug delivery systems, stem cell therapies, and tissue-engineered scaffolds in more detail. Full article

(This article belongs to the Special Issue Highlights in Pathophysiology of the Musculoskeletal System, 2nd Edition)

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17 pages, 2927 KiB

Open AccessReview

Knee Osteoarthritis: Epidemiology, Pathogenesis, and Mesenchymal Stem Cells: What Else Is New? An Update

by Riccardo Giorgino, Domenico Albano, Stefano Fusco, Giuseppe M. Peretti, Laura Mangiavini and Carmelo Messina

Int. J. Mol. Sci. 2023, 24(7), 6405; https://doi.org/10.3390/ijms24076405 - 29 Mar 2023

Cited by 166 | Viewed by 17923

Abstract

Osteoarthritis (OA) is a chronic disease and the most common orthopedic disorder. A vast majority of the social OA burden is related to hips and knees. The prevalence of knee OA varied across studies and such differences are reflected by the heterogeneity of [...] Read more.

Osteoarthritis (OA) is a chronic disease and the most common orthopedic disorder. A vast majority of the social OA burden is related to hips and knees. The prevalence of knee OA varied across studies and such differences are reflected by the heterogeneity of data reported by studies conducted worldwide. A complete understanding of the pathogenetic mechanisms underlying this pathology is essential. The OA inflammatory process starts in the synovial membrane with the activation of the immune system, involving both humoral and cellular mediators. A crucial role in this process is played by the so-called “damage-associated molecular patterns” (DAMPs). Mesenchymal stem cells (MSCs) may be a promising option among all possible therapeutic options. However, many issues are still debated, such as the best cell source, their nature, and the right amount. Further studies are needed to clarify the remaining doubts. This review provides an overview of the most recent and relevant data on the molecular mechanism of cartilage damage in knee OA, including current therapeutic approaches in regenerative medicine. Full article

(This article belongs to the Special Issue Highlights in Pathophysiology of the Musculoskeletal System, 2nd Edition)

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