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Biomedicines
Special Issues
Musculoskeletal Diseases: From Molecular Basis to Therapy—3rd Edition
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Musculoskeletal Diseases: From Molecular Basis to Therapy—3rd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 3549

Special Issue Editors

Dr. Elisa Belluzzi

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Guest Editor
1. Musculoskeletal Pathology and Oncology Laboratory, Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35129 Padova, Italy
2. Orthopedics and Orthopedic Oncology, Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35129 Padova, Italy
Interests: inflammation; molecular biology; cell biology; osteoarthritis; cartilage; musculoskeletal diseases; bone cancer; synovium; infrapatellar fat pad; chondrosarcoma
Special Issues, Collections and Topics in MDPI journals
Dr. Assunta Pozzuoli

E-Mail Website
Guest Editor
1. Musculoskeletal Pathology and Oncology Laboratory, Orthopaedic and Traumatologic Clinic, Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128 Padova, Italy
2. Orthopedics and Orthopedic Oncology, Department of Surgery, Oncology and Gastroenterology (DiSCOG), University-Hospital of Padova, 35128 Padova, Italy
Interests: musculoskeletal diseases; bone cancer; chondrosarcoma; osteoarthritis; inflammation; joint tissues; aging; molecular biology; cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Musculoskeletal diseases comprise numerous different disorders (more than 150 conditions) that affect the locomotor system (joints, bones, muscles, cartilage, menisci, and tendon tissues) and are associated with significant morbidity and disability. A recent analysis of the Global Burden of Disease estimated that approximately 1.71 billion people globally have musculoskeletal conditions. The number of affected individuals is expected to grow as the population ages. Thus, a better understanding of the etiology and new and more effective therapeutic treatments are needed. The purpose of this Special Issue is to report advances in pathophysiological mechanisms, predictive biomarkers, and preclinical therapeutic approaches in musculoskeletal disorders, with a particular focus on bone cancers and osteoarthritis.

Authors are invited to contribute to this Special Issue by sharing original research articles and comprehensive reviews.

Possible topics include, but are not limited to, the following:

  • Pathophysiological studies related to musculoskeletal diseases;
  • Molecular, biochemical, and biomechanical mechanisms involved in the etiology and progression of musculoskeletal disorders;
  • The identification of biomarkers that are useful for early diagnosis and/or predictive of prognosis;
  • Preclinical research into potential drugs and cell-based strategies for the treatment of musculoskeletal disorders.

Dr. Elisa Belluzzi
Dr. Assunta Pozzuoli
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. Biomedicines 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 2600 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

  • musculoskeletal diseases
  • bone cancer
  • soft tissue cancer
  • bone metastasis
  • natural compounds
  • anticancer drugs
  • osteoarthritis
  • joint tissues
  • biomarkers
  • inflammation
  • microRNAs
  • exosomes

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Related Special Issues

Published Papers (3 papers)

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Research

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18 pages, 2994 KB  
Article
Altered Expression of Cell Cycle Regulators and Factors Released by Aged Cells in Skeletal Muscle of Patients with Bone Fragility: A Pilot Study on the Potential Role of SIRT1 in Muscle Atrophy
by Angela Falvino, Roberto Bonanni, Beatrice Gasperini, Ida Cariati, Angela Chiavoghilefu, Amarildo Smakaj, Virginia Veronica Visconti, Annalisa Botta, Riccardo Iundusi, Elena Gasbarra, Virginia Tancredi and Umberto Tarantino
Biomedicines 2025, 13(6), 1350; https://doi.org/10.3390/biomedicines13061350 - 31 May 2025
Cited by 1 | Viewed by 1035
Abstract
Background/Objectives: Cellular aging represents a crucial element in the progression of musculoskeletal diseases, contributing to muscle atrophy, functional decline, and alterations in bone turnover, which promote fragility fractures. However, knowledge about expression patterns of factors potentially involved in aging and senescence at [...] Read more.
Background/Objectives: Cellular aging represents a crucial element in the progression of musculoskeletal diseases, contributing to muscle atrophy, functional decline, and alterations in bone turnover, which promote fragility fractures. However, knowledge about expression patterns of factors potentially involved in aging and senescence at the tissue level remains limited. Our pilot study aimed to characterize the expression profile of cell cycle regulators, factors released by aged cells, and sirtuin 1 (SIRT1) in the muscle tissue of 26 elderly patients undergoing hip arthroplasty, including 13 with low-energy fracture and 13 with osteoarthritis (OA). Methods: The mRNA expression levels of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), cyclin-dependent kinase inhibitor 2A (CDKN2A), p53, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-15 (IL-15), chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3), growth differentiation factor 15 (GDF15), and SIRT1 were evaluated in muscle tissue by qRT-PCR. In addition, immunohistochemistry and Western blotting analysis were conducted to measure the protein levels of SIRT1. Results: A marked muscle atrophy was observed in fractured patients compared to the OA group, in association with an up-regulation of cell cycle regulators and factors released by the aged cells. The expression of matrix metallopeptidase 3 (MMP3), plasminogen activator inhibitor 1 (PAI-1), and fas cell surface death receptor (FAS) was also investigated, although no significant differences were observed between the two experimental groups. Notably, SIRT1 expression was significantly higher in OA patients, confirming its role in maintaining muscle health during aging. Conclusions: Further studies will be needed to clarify the role of SIRT1 in the senescence characteristic of age-related musculoskeletal disorders, counteracting the muscle atrophy that predisposes to fragility fractures. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy—3rd Edition)
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Review

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38 pages, 3048 KB  
Review
Mitochondria as a Disease-Relevant Organelle in Rheumatoid Arthritis: A Key Breakout in Fight Against the Disease
by Antonella Iaconis, Francesco Molinari, Roberta Fusco and Rosanna Di Paola
Biomedicines 2025, 13(7), 1708; https://doi.org/10.3390/biomedicines13071708 - 13 Jul 2025
Viewed by 858
Abstract
Rheumatoid arthritis (RA) is one of the most representative autoimmune diseases. The peculiarity of this disease is synovial inflammation, which results in joint destruction and often disability. Although there are still several pathogenetic mechanisms to be clarified, lately, most studies have highlighted the [...] Read more.
Rheumatoid arthritis (RA) is one of the most representative autoimmune diseases. The peculiarity of this disease is synovial inflammation, which results in joint destruction and often disability. Although there are still several pathogenetic mechanisms to be clarified, lately, most studies have highlighted the involvement of mitochondria in the onset and progression of the disease. Mitochondrial functions are connected to many metabolic processes and the delivery of proinflammatory mediators. Mitochondria play a crucial role in the physiopathology of RA, contributing to chronic inflammation, cartilage and bone injury and chronic autoimmune response. Mitochondrial activity influences many aspects of the disease that will be discussed in terms of their correlation with the onset and persistence of RA, starting from mitochondrial dynamics up to bone homeostasis, passing through DAMPs and affecting immune cell functionality. Recent therapeutic approaches aim to improve mitochondrial function, reduce oxidative stress, modulate mitochondria-mediated inflammation and restore energy metabolism homeostasis. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy—3rd Edition)
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33 pages, 1902 KB  
Review
Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization
by Alhomam Dabaliz, Hagar Mahmoud, Raffi AlMutawa and Khalid S. Mohammad
Biomedicines 2025, 13(7), 1640; https://doi.org/10.3390/biomedicines13071640 - 4 Jul 2025
Viewed by 1109
Abstract
Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer [...] Read more.
Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homing to mineralized tissues. We then outline the sequential establishment of the pre-metastatic niche, driven by EV-mediated processes including fibronectin deposition, stromal cell reprogramming, angiogenesis, neurogenesis, metabolic reconfiguration, and immune modulation, specifically, the expansion of myeloid-derived suppressor cells and impaired lymphocyte function. Within the bone microenvironment, tumor-derived EVs carrying microRNAs and proteins shift the balance toward osteoclastogenesis, inhibit osteoblast differentiation, and disrupt osteocyte signaling. These alterations promote osteolytic destruction or aberrant bone formation depending on tumor type. We also highlight cutting-edge imaging modalities and single-EV omics technologies that resolve EV heterogeneity and identify potential biomarkers detectable in plasma and urine. Finally, we explore therapeutic approaches targeting EVs, such as inhibition of nSMase2 or Rab27A, extracorporeal EV clearance, and delivery of engineered, bone-targeted vesicles, while addressing translational challenges and regulatory considerations. This review offers a roadmap for leveraging EV biology in predicting, preventing, and treating skeletal metastases by integrating advances across basic biology, bioengineering, and translational science. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy—3rd Edition)
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