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Biomedicines
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Molecular Insights and Translational Approaches in Musculoskeletal Disorders
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Molecular Insights and Translational Approaches in Musculoskeletal Disorders

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

Deadline for manuscript submissions: closed (31 October 2025) | Viewed by 3573

Special Issue Editor

Dr. Priyanka Kushwaha

E-Mail Website
Guest Editor
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Interests: rheumatoid arthritis; bone remodeling; osteoblast; osteocyte; osteoclast; fibroblast; synovium; macrophage cells; metabolism-related bone diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Musculoskeletal disorders (MSDs) are a worldwide health problem that impact bones, joints, and adjacent tissues like muscles, nerves, and blood vessels. This pathological condition can arise due to various factors like metabolic disorders, inflammation, genetic disease, cancer, aging, and infections. To understand the underlying molecular mechanism of musculoskeletal disorders (MSDs) and their impact on the skeletal system and neighboring tissues, we invite original research articles, reviews, and novel ideas from basic and clinical research. We encourage submissions on the following topics:  

  • Molecular mechanisms driving musculoskeletal diseases such as osteoarthritis, rheumatoid arthritis, osteoporosis, and muscular dystrophy.
  • Genetic and epigenetic regulation in the pathogenesis of musculoskeletal disorders.
  • Role of microbiota and systemic inflammation in maintaining bone homeostasis.
  • Translational research focusing on developing targeted therapies, including stem cell therapy, regenerative medicine, and miRNA/siRNA-based treatments.
  • Impact of metabolism and energy regulation on musculoskeletal health.
  • Innovative animal models for studying musculoskeletal disorders.
  • Crosstalk between immune cells and bone cells contributing to bone loss.

Dr. Priyanka Kushwaha
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 250 words) can be sent to the Editorial Office for assessment.

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 disorders
  • osteoarthritis
  • rheumatoid arthritis

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Published Papers (5 papers)

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Research

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20 pages, 2921 KB  
Article
In Vitro Osteogenic Stimulation of Human Adipose-Derived MSCs on Biofunctional 3D-Printed Scaffolds
by Serena Munaò, Ugo D’Amora, Luana Vittoria Bauso, Alfredo Ronca, Paola Manini, Alessandro Pezzella, Maria Grazia Raucci, Luigi Ambrosio and Giovanna Calabrese
Biomedicines 2025, 13(11), 2755; https://doi.org/10.3390/biomedicines13112755 - 11 Nov 2025
Cited by 1 | Viewed by 807
Abstract
Background: Human adipose-derived mesenchymal stem cells (hADMSCs) are widely used in regenerative medicine due to their ability to proliferate and differentiate. Bone tissue engineering represents an innovative alternative to traditional grafts by combining biomimetic materials, stem cells, and bioactive factors to promote bone [...] Read more.
Background: Human adipose-derived mesenchymal stem cells (hADMSCs) are widely used in regenerative medicine due to their ability to proliferate and differentiate. Bone tissue engineering represents an innovative alternative to traditional grafts by combining biomimetic materials, stem cells, and bioactive factors to promote bone regeneration. Gellan gum (GG) is a promising scaffold material owing to its excellent biocompatibility and favorable physicochemical characteristics; however, chemical modifications such as methacrylation are necessary to enhance its mechanical strength and long-term stability. In this in vitro study, osteoprogenitor cells are cultured for 21 days on three 3D-printed GGMA-based scaffolds to evaluate their biological response: (i) neat GGMA, (ii) GGMA functionalized with hydroxyapatite (HAp), and (iii) GGMA functionalized with eumelanin derived from black soldier fly (BSF-Eumelanin). Methods: Cell adhesion, viability, proliferation and osteogenic differentiation are evaluated using MTT assays, histological staining (H&E and Alizarin Red S), alkaline phosphatase (ALP) activity, and gene expression analysis of key osteogenic markers. Results: Our results show that all GGMA-based scaffolds support cell adhesion, growth, and proliferation, while BSF-Eumelanin and HAp notably enhance osteogenic differentiation compared to neat GGMA. Conclusions: These findings highlight the potential of embedding bioactive factors into GGMA scaffolds to improve osteoconductive and osteoinductive performance, offering a promising strategy for bone repair. Full article
(This article belongs to the Special Issue Molecular Insights and Translational Approaches in Musculoskeletal Disorders)
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Review

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10 pages, 538 KB  
Review
What Is Inside the Sinus Tarsi? Mechanoreceptor Distribution, Typing and Clinical Relevance—A Histological and Immunohistochemical Synthesis
by Alberto Arceri, Antonio Mazzotti, Gianmarco Di Paola, Federico Sgubbi, Laura Langone, Simone Ottavio Zielli, Francesca Veronesi, Gianluca Giavaresi, Paolo Mora and Cesare Faldini
Biomedicines 2025, 13(12), 3052; https://doi.org/10.3390/biomedicines13123052 - 11 Dec 2025
Viewed by 99
Abstract
The sinus tarsi, a small osseoligamentous recess of the subtalar joint, contains multiple soft-tissue structures with a complex sensory network. However, the detailed neural architecture and clinical significance of its innervation remain incompletely defined. The aim of this study was to conduct a [...] Read more.
The sinus tarsi, a small osseoligamentous recess of the subtalar joint, contains multiple soft-tissue structures with a complex sensory network. However, the detailed neural architecture and clinical significance of its innervation remain incompletely defined. The aim of this study was to conduct a comprehensive review of histological and immunohistochemical studies on the neural structures of the sinus tarsi. Histological staining and validated immunohistochemical markers (S100, p75, PGP9.5, neurofilament, myelin basic protein) were the methods used in these studies to analyze human sinus tarsi tissue. Across all investigations, free nerve endings predominated, while Ruffini, Pacinian and Golgi-like corpuscles were variably identified, mainly near ligament insertions. The sinus tarsi exhibits a dense and heterogeneous neural network that likely contributes to both pain perception and sensorimotor control. Further standardized and quantitative research is warranted to clarify the neurofunctional role of this region. Full article
(This article belongs to the Special Issue Molecular Insights and Translational Approaches in Musculoskeletal Disorders)
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29 pages, 717 KB  
Review
Novel Translational Concept: Axon-to-Muscle Exosomal Signaling as an Emerging Therapeutic Target in Spinal Muscular Atrophy
by Almir Fajkić, Andrej Belančić, Yun Wah Lam, Valentino Rački, Kristina Pilipović, Tamara Janković, Silvestar Mežnarić, Jasenka Mršić-Pelčić and Dinko Vitezić
Biomedicines 2025, 13(12), 2876; https://doi.org/10.3390/biomedicines13122876 - 25 Nov 2025
Viewed by 562
Abstract
Spinal muscular atrophy (SMA) has transitioned from a uniformly fatal disease to a treatable condition, yet incomplete neuromuscular recovery underscores the limits of current SMN-restorative therapies. Emerging data implicate disrupted axon-to-muscle exosomal signaling as an important, overlooked driver of residual dysfunction. Exosomes, nanovesicles [...] Read more.
Spinal muscular atrophy (SMA) has transitioned from a uniformly fatal disease to a treatable condition, yet incomplete neuromuscular recovery underscores the limits of current SMN-restorative therapies. Emerging data implicate disrupted axon-to-muscle exosomal signaling as an important, overlooked driver of residual dysfunction. Exosomes, nanovesicles mediating bidirectional neuronal-muscular communication, carry synaptic organizers, trophic factors, and microRNAs essential for neuromuscular junction integrity. SMN deficiency alters exosomal biogenesis and cargo, leading to loss of agrin-MuSK signaling, impaired β-actin transport, and muscle atrophy. Comparative insights from amyotrophic lateral sclerosis and muscular dystrophy reveal that stem-cell-derived or engineered exosomes restore synaptic stability, enhance regeneration, and cross biological barriers safely. Thus, we speculate herein on a translational model integrating exosome-based therapies with existing genetic interventions to achieve durable, systems-level recovery in SMA. Exosomal profiling may further yield minimally invasive biomarkers for disease monitoring and treatment optimization, establishing vesicle-mediated communication as a novel therapeutic axis in neuromuscular medicine. Full article
(This article belongs to the Special Issue Molecular Insights and Translational Approaches in Musculoskeletal Disorders)
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47 pages, 5619 KB  
Review
Iron-Related Metabolic Targets in the Treatment of Osteosarcoma: Research Progress and Prospects
by Arianna Buglione, Magda Gioia, Federica Sinibaldi, Stefano Marini and Chiara Ciaccio
Biomedicines 2025, 13(11), 2756; https://doi.org/10.3390/biomedicines13112756 - 11 Nov 2025
Viewed by 576
Abstract
Iron metabolism has emerged as a critical regulator of cancer biology, with mounting evidence linking iron dysregulation to tumor initiation, progression, and resistance mechanisms. Osteosarcoma (OS) is the most common primary bone malignancy and a leading cause of cancer-related death in children and [...] Read more.
Iron metabolism has emerged as a critical regulator of cancer biology, with mounting evidence linking iron dysregulation to tumor initiation, progression, and resistance mechanisms. Osteosarcoma (OS) is the most common primary bone malignancy and a leading cause of cancer-related death in children and young adults; recent studies have identified profound alterations in iron homeostasis at both cellular and microenvironmental levels in OS. These include increased iron uptake, disrupted storage and export, and a reliance on iron-dependent metabolic pathways that promote proliferation, metastasis, and immune evasion. Despite advances in surgical and chemotherapeutic approaches, survival outcomes in OS have stagnated, underscoring the need for novel therapeutic strategies. Targeting iron metabolism represents a promising avenue, with strategies such as iron chelation, transferring receptor inhibition, ferroptosis induction, and modulation of ferritinophagy, showing preclinical efficacy. In this review, we provide an updated and integrated overview of the multifaceted role of iron in OS pathogenesis, dissect emerging therapeutic approaches aimed at disrupting iron regulatory networks, and highlight innovative delivery platforms including nanomedicine. By integrating current insights on iron metabolism with the molecular complexity of OS, we present a comprehensive perspective, while acknowledging that the limited clinical translatability of current findings still hinders progress toward clinical application. A deeper understanding of iron-driven mechanisms may guide future studies toward the development of safe and effective iron-targeted therapies for OS. Full article
(This article belongs to the Special Issue Molecular Insights and Translational Approaches in Musculoskeletal Disorders)
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Other

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16 pages, 297 KB  
Perspective
Regenerative and Drug-Free Strategies for Chronic Musculoskeletal Pain: An Evidence-Based Perspective on Shockwave Therapy, High-Intensity Laser Therapy and Ultrasound-Guided Mechanical Needling with Sterile Water Injection
by Carl P. C. Chen and Areerat Suputtitada
Biomedicines 2025, 13(11), 2801; https://doi.org/10.3390/biomedicines13112801 - 17 Nov 2025
Viewed by 993
Abstract
Chronic musculoskeletal pain (CMP) is the leading global cause of disability and a major contributor to healthcare burden. Its pathogenesis reflects regenerative failure, driven by extracellular matrix (ECM) fibrosis, calcific deposition, mitochondrial dysfunction, and neuroimmune sensitization. Conventional pharmacological therapies such as NSAIDs, corticosteroids, [...] Read more.
Chronic musculoskeletal pain (CMP) is the leading global cause of disability and a major contributor to healthcare burden. Its pathogenesis reflects regenerative failure, driven by extracellular matrix (ECM) fibrosis, calcific deposition, mitochondrial dysfunction, and neuroimmune sensitization. Conventional pharmacological therapies such as NSAIDs, corticosteroids, and opioids offer only transient symptomatic relief while exposing patients to systemic complications. In contrast, energy-based, drug-free regenerative interventions directly address underlying pathology and restore physiological function. This Perspective synthesizes recent evidence (2020–2025) on three modalities that together form a regenerative triad: extracorporeal shockwave therapy (ESWT), high-intensity laser therapy (HILT), and ultrasound-guided mechanical needling with sterile water injection (SWI). ESWT promotes mechanotransduction, angiogenesis, and ECM remodeling; HILT enhances mitochondrial bioenergetics and downregulates inflammatory pathways; and SWI disrupts fibrosis and calcification while restoring neurovascular dynamics. Evidence from randomized controlled trials and meta-analyses supports moderate-to-high certainty (GRADE B–A–) for ESWT and HILT. SWI, initially supported by large observational cohorts and comparative studies, is now reinforced by a randomized comparative trial and meta-analyses of lavage effects, justifying an upgrade from moderate (B) to moderate-to-high certainty (B–A–). Risk of bias assessment using Cochrane RoB 2.0 and the Newcastle–Ottawa Scale (NOS) indicates overall low-to-moderate concerns across modalities. Together, these interventions integrate mechanistic biology with translational rehabilitation practice. This Perspective outlines their mechanistic foundations, clinical evidence, and alignment with the WHO decade of healthy ageing, offering a drug-free, mechanism-based framework for sustainable CMP management. Full article
(This article belongs to the Special Issue Molecular Insights and Translational Approaches in Musculoskeletal Disorders)
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