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Musculoskeletal Disease: From Molecular Basis to Therapy
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Musculoskeletal Disease: From Molecular Basis to Therapy

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: 20 May 2025 | Viewed by 5114

Special Issue Editor

Dr. Ioannis Kanakis

E-Mail Website
Guest Editor
Chester Medical School, University of Chester, Bache Hall, Countess View, Chester CH2 1BR, UK
Interests: clinical biochemistry; bone metastases; musculoskeletal ageing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Musculoskeletal diseases comprise a diverse range of bone, joint, muscle and connective tissue pathologies and affect all genders, races, and ethnicities. The treatment approaches available for musculoskeletal disorders have substantially progressed in the last decades, especially in terms of pain management and tissue regeneration. However, the puzzle of the pathogenetic mechanisms has not yet been solved, although significant steps have been made, especially in the -omics era, and these developments are a means to fully understand pathobiology with the purpose of producing effective therapeutics.

This Special Issue of IJMS, entitled ‘Musculoskeletal Disease: From Molecular Basis to Therapy’, is led by Dr. Ioannis Kanakis and aims to focus on new insights, novel developments and discoveries, current challenges, and future perspectives in the field of musculoskeletal diseases.

Dr. Ioannis Kanakis
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 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. 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

  • musculoskeletal diseases
  • osteoporosis
  • osteoarthritis
  • sarcopenia
  • molecular mechanisms

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Published Papers (3 papers)

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Research

14 pages, 1469 KiB  
Article
Loss of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Regulation and Limits Exercise Capacity
by Ji-Hyun Lee, Ik-Rak Jung, Becky Tu-Sekine, Sunghee Jin, Frederick Anokye-Danso, Rexford S. Ahima and Sangwon F. Kim
Int. J. Mol. Sci. 2025, 26(6), 2395; https://doi.org/10.3390/ijms26062395 - 7 Mar 2025
Viewed by 462
Abstract
Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways, and inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is [...] Read more.
Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways, and inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is still poorly understood. Since skeletal muscle is a major contributor to energy homeostasis, we have developed a mouse model in which skeletal muscle IPMK is specifically deleted and examined how a loss of IPMK affects whole-body metabolism. Here, we report that skeletal-muscle-specific IPMK knockout mice exhibited a ~12% increase in body weight compared to WT controls (p < 0.05). These mice also showed a significantly impaired glucose tolerance, as indicated by their ~50% higher blood glucose levels during GTT. Additionally, exercise capacity was reduced by ~45% in IPMK-MKO mice, demonstrating a decline in endurance. Moreover, these metabolic alterations were accompanied by a 2.5-fold increase in skeletal muscle triglyceride accumulation, suggesting impaired lipid metabolism. Further analysis revealed that IPMK-deficient myocytes exhibited 30% lower β-oxidation rates. Thus, our results suggest that IPMK mediates whole-body metabolism by regulating muscle metabolism and may be potentially targeted for the treatment of metabolic syndromes. Full article
(This article belongs to the Special Issue Musculoskeletal Disease: From Molecular Basis to Therapy)
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14 pages, 5104 KiB  
Article
Novel Method for the Rapid Establishment of Antibiotic Susceptibility Profiles in Bacterial Strains Linked to Musculoskeletal Infections Using Scattered Light Integrated Collector Technology
by Damien Bertheloot, Vincent B. Nessler, Elio Assaf, Cosmea F. Amerschläger, Kani Ali, Robert Ossendorff, Max Jaenisch, Andreas C. Strauss, Christof Burger, Phillip J. Walmsley, Gunnar T. Hischebeth, Dieter C. Wirtz, Robert J. H. Hammond and Frank A. Schildberg
Int. J. Mol. Sci. 2025, 26(4), 1553; https://doi.org/10.3390/ijms26041553 - 12 Feb 2025
Viewed by 720
Abstract
Bacterial antibiotic resistance is an important challenge that the healthcare system is continually battling and a major problem in the treatment of musculoskeletal infections such as periprosthetic joint infections. Current methods to identify infectious microbes and define susceptibility to antibiotics require two to [...] Read more.
Bacterial antibiotic resistance is an important challenge that the healthcare system is continually battling and a major problem in the treatment of musculoskeletal infections such as periprosthetic joint infections. Current methods to identify infectious microbes and define susceptibility to antibiotics require two to ten days from isolation to the establishment of an antibiogram. This slow process limits advances in antimicrobial drug discovery and, in the clinical context, delays the delivery of targeted treatments, with potentially devastating outcomes for patients. With this in mind, we strived to establish a quicker and more sensitive method to deliver antibiotic susceptibility profiles of clinically relevant microbes using Scattered Light Integrated Collector (SLIC) technology. We established antibiotic panels to obtain an approximate identification of a wide variety of microbes linked to periprosthetic joint infections and determine their susceptibility to antibiotics. We challenged microbes isolated from patients with our tailored antibiotic panels and found that SLIC detects perturbations in bacterial growth accurately and reproducibly within minutes of culture. Indeed, we could show that SLIC can be used to measure the dose-dependent inhibitory or bacteriolytic activity of broad classes of antibiotics. Our panel design enabled us to establish a profile similar to an antibiogram for the tested bacteria within 90 min. Our method can provide information on the class of bacteria tested and potential treatment avenues in parallel. Our proof-of-principle experiments using isolated clinical strains of bacteria demonstrate that SLIC, together with our specifically designed antibiotic panels, could be used to rapidly provide information on the identity of an infecting microbe, such as those associated with periprosthetic joint infections, and guide physicians to prescribe targeted antibiotic treatment early-on. The constant emergence of resistant strains of bacteria pushes the pharmaceutical industry to develop further effective drugs. Our optimized method could significantly accelerate this work by characterizing the efficacy of new classes of compounds against bacterial viability within minutes, a timeframe far shorter than the current standards. Full article
(This article belongs to the Special Issue Musculoskeletal Disease: From Molecular Basis to Therapy)
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16 pages, 39589 KiB  
Article
Defining the Most Potent Osteoinductive Culture Conditions for MC3T3-E1 Cells Reveals No Implication of Oxidative Stress or Energy Metabolism
by Alexandra Semicheva, Ufuk Ersoy, Aphrodite Vasilaki, Ioanna Myrtziou and Ioannis Kanakis
Int. J. Mol. Sci. 2024, 25(8), 4180; https://doi.org/10.3390/ijms25084180 - 10 Apr 2024
Cited by 1 | Viewed by 3030
Abstract
The MC3T3-E1 preosteoblastic cell line is widely utilised as a reliable in vitro system to assess bone formation. However, the experimental growth conditions for these cells hugely diverge, and, particularly, the osteogenic medium (OSM)’s composition varies in research studies. Therefore, we aimed to [...] Read more.
The MC3T3-E1 preosteoblastic cell line is widely utilised as a reliable in vitro system to assess bone formation. However, the experimental growth conditions for these cells hugely diverge, and, particularly, the osteogenic medium (OSM)’s composition varies in research studies. Therefore, we aimed to define the ideal culture conditions for MC3T3-E1 subclone 4 cells with regard to their mineralization capacity and explore if oxidative stress or the cellular metabolism processes are implicated. Cells were treated with nine different combinations of long-lasting ascorbate (Asc) and β-glycerophosphate (βGP), and osteogenesis/calcification was evaluated at three different time-points by qPCR, Western blotting, and bone nodule staining. Key molecules of the oxidative and metabolic pathways were also assessed. It was found that sufficient mineral deposition was achieved only in the 150 μg.mL−1/2 mM Asc/βGP combination on day 21 in OSM, and this was supported by Runx2, Alpl, Bglap, and Col1a1 expression level increases. NOX2 and SOD2 as well as PGC1α and Tfam were also monitored as indicators of redox and metabolic processes, respectively, where no differences were observed. Elevation in OCN protein levels and ALP activity showed that mineralisation comes as a result of these differences. This work defines the most appropriate culture conditions for MC3T3-E1 cells and could be used by other research laboratories in this field. Full article
(This article belongs to the Special Issue Musculoskeletal Disease: From Molecular Basis to Therapy)
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