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Musculoskeletal Disorders: From Molecular Pathology to Novel Therapeutic Approach—2nd Edition
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Musculoskeletal Disorders: From Molecular Pathology to Novel Therapeutic Approach—2nd Edition

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: 31 July 2026 | Viewed by 1162

Special Issue Editor

Prof. Dr. María Orosia Lucha López

E-Mail Website
Guest Editor
Unidad de Investigación en Fisioterapia, Facultad de Ciencias de la Salud, Universidad de Zaragoza, Domingo Miral, s/n, 50009 Zaragoza, Spain
Interests: physiotherapy; musculoskeletal disorders; dry needling; manual therapy; instrumentally assisted manual therapy; therapeutic exercise
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Musculoskeletal disorders are one of the most prevalent pathologies worldwide and may affect a diversity of tissular organizations conforming to the structural components of the neuromusculoskeletal system. The prevalence of these pathologies, particularly those with a chronic nature, seems to be on the rise, raising concerns regarding the older average age of the population and certain lifestyle habits, such as a sedentary lifestyle, which determine a physiological state that is prone to the appearance and chronicity of this type of pathology. A sedentary lifestyle leads to a destabilization of cellular homeostasis, which is linked to major macroscopic dysfunctions, such as obesity, but also to imbalances in tissue functioning that can favor the chronicity of musculoskeletal disorders. 

This will be led by Prof. Dr. María Orosia Lucha-López and assisted by our Topical Advisory Panel Member Dr. Clemens Gögele (Paracelsus Medical University). This Special Issue of IJMS, entitled “Musculoskeletal Disorders: From Molecular Pathology to Novel Therapeutic Approach—2nd Edition”, aims to consolidate research highlighting new insights into the pathological mechanisms underlying the regenerative failure of musculoskeletal system tissues. In addition, this Special Issue will cover emerging artificial intelligence-based and neuroscience-related approaches, particularly those that contribute to a better understanding of neuromuscular interactions, pain processing, motor control, and tissue regeneration in musculoskeletal disorders. New evidence based on AI-driven analyses, computational modeling, and neurobiological perspectives, together with novel therapeutic strategies whose mechanisms of action are becoming clearer thanks to recent advances in molecular pathology and neuroscience, will enrich future prevention, diagnosis, and treatment of musculoskeletal disorders.

Prof. Dr. María Orosia Lucha López
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • joints
  • skeletal muscles
  • tendons
  • ligaments
  • fascia
  • articular cartilage
  • intervertebral discs
  • physiotherapy
  • novel therapies

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Published Papers (2 papers)

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Research

16 pages, 1853 KB  
Article
Pathway-Level Reorganization of Genetic Signals Associated with Low Bone Mineral Density Across the Menopausal Transition
by Soo-Eun Choi, Su Kang Kim, Gyutae Kim, Ju Yeon Ban and Sang Wook Kang
Int. J. Mol. Sci. 2026, 27(10), 4447; https://doi.org/10.3390/ijms27104447 (registering DOI) - 15 May 2026
Abstract
Osteoporosis in women is strongly influenced by menopause, a major physiological transition that reshapes bone metabolism. Although low bone mineral density (BMD) in premenopausal women and osteoporosis in postmenopausal women share the clinical outcome of skeletal fragility, it remains unclear whether they reflect [...] Read more.
Osteoporosis in women is strongly influenced by menopause, a major physiological transition that reshapes bone metabolism. Although low bone mineral density (BMD) in premenopausal women and osteoporosis in postmenopausal women share the clinical outcome of skeletal fragility, it remains unclear whether they reflect a shared molecular program or distinct regulatory mechanisms. Here, we compared genetic signals associated with premenopausal and postmenopausal low BMD in Korean women using two independent genotyping platforms with distinct variant coverage. After allele harmonization and heterogeneity testing, variants were classified as reversal signals, showing directionally discordant effects across menopausal status, or stable signals, showing concordant effects. Gene-level association analysis was performed using Multi-marker Analysis of GenoMic Annotation (MAGMA), followed by functional enrichment and network-based analyses. Reversal and stable signals showed distinct biological patterns. Reversal signals consistently converged on cyclic nucleotide-related pathways, including cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) signaling and nitric oxide-mediated processes, whereas stable signals were more broadly distributed across pathways related to ion homeostasis, cell–substrate adhesion, and structural maintenance. These pathway-level patterns were reproducible across platforms despite limited SNP-level overlap. These findings suggest that low BMD across the menopausal transition is better resolved at the gene and pathway levels than at the level of individual SNPs. Full article
(This article belongs to the Special Issue Musculoskeletal Disorders: From Molecular Pathology to Novel Therapeutic Approach—2nd Edition)
17 pages, 1638 KB  
Article
Molecular Hydrogen Reverses Nociplastic Pain and Depressive-like Behaviors via Region- and Sex-Dependent Central Mechanisms
by Sylmara Esther Negrini-Ferrari, Ignacio Martínez-Martel and Olga Pol
Int. J. Mol. Sci. 2026, 27(7), 3051; https://doi.org/10.3390/ijms27073051 - 27 Mar 2026
Viewed by 854
Abstract
Fibromyalgia is a chronic nociplastic pain condition frequently accompanied by affective disturbances, particularly depression, for which effective treatments remain limited. Increasing evidence implicates central oxidative stress, maladaptive synaptic plasticity, and neuroinflammatory alterations in its pathophysiology. This study investigated the therapeutic effects of molecular [...] Read more.
Fibromyalgia is a chronic nociplastic pain condition frequently accompanied by affective disturbances, particularly depression, for which effective treatments remain limited. Increasing evidence implicates central oxidative stress, maladaptive synaptic plasticity, and neuroinflammatory alterations in its pathophysiology. This study investigated the therapeutic effects of molecular hydrogen (H2) in a reserpine-induced murine model of fibromyalgia, with emphasis on sex-dependent and region-specific mechanisms. Male and female C57BL/6 mice received repeated reserpine injections to induce fibromyalgia-like symptoms. Mechanical allodynia, thermal hyperalgesia, cold allodynia, and depressive-like behaviors were assessed, followed by molecular analyses in the spinal cord and amygdala. Reserpine induced persistent nociceptive hypersensitivity and depressive-like behaviors in both sexes, with earlier cold allodynia in females. Hydrogen-rich water (HRW) progressively reversed mechanical and thermal hypersensitivity and rapidly abolished cold allodynia, showing greater efficacy in females. HRW also normalized depressive-like behaviors in both sexes. At the molecular level, HRW reduced spinal oxidative stress and ERK-dependent plasticity without altering spinal NLRP3 expression, whereas it fully reversed NLRP3 upregulation and HO-1 downregulation in the amygdala. HRW additionally engaged sex-dependent antioxidant pathways in the spinal cord. These findings indicate that H2 alleviates sensory and affective alterations through region- and sex-dependent central mechanisms, supporting HRW as a promising therapeutic strategy for nociplastic pain and its affective comorbidities. Full article
(This article belongs to the Special Issue Musculoskeletal Disorders: From Molecular Pathology to Novel Therapeutic Approach—2nd Edition)
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