Search Results (459)

Sports injuries, especially musculoskeletal and neurological types from strenuous exercise, are a global public health challenge. Characterized by a high incidence and slow recovery, these injuries differ from typical trauma, often resulting in severe mechanical transmission loss and an imbalanced immune microenvironment. Consequently, standard interventions struggle to achieve true tissue regeneration. Gelatin, a collagen-derived biomaterial, offers RGD-mediated cell adhesion, MMP-responsive degradation, and high modifiability. These qualities make it an excellent foundation for biomimetic repair scaffolds. This paper reviews the design principles and recent advances in gelatin-based multifunctional hydrogels in sports medicine. First, we analyse their structure and engineering advantages. Next, we summarise strategies and mechanisms for modules like conductivity, antibacterial activity, self-healing, stimulus responsiveness, and tissue adhesion. The review links these modules to types of injuries: bone or cartilage, tendon or ligament, skeletal muscle, spinal cord, and peripheral nerve. It clarifies their clinical and translational value in remodelling immune microenvironments, regulating electrophysiology, promoting interfacial regeneration, and restoring motor function. This review provides focused insights from materials science and sports rehabilitation to advance precision treatments for sports injuries. Full article

In skeletal muscle, there are two main progenitor populations crucial for growth, maintenance, and repair: satellite cells (SCs) and interstitial cells, of which fibro-adipogenic progenitor cells (FAPs) are the best characterized fraction. However, data on how specific diseases or physiological conditions affect the biological properties of FAPs are limited. In this review we analyze data obtained with FAPs purified from skeletal muscle tissue from Duchenne muscular dystrophy (both human patients and mdx mice models), hindlimb functional unloading (rats), and type 2 diabetes (T2DM, human patients). Here we discuss how disuse/disease affect FAP’s properties: the adaptive metabolic remodeling; the alterations in adipogenic differentiation in vitro; the possible role of particular subpopulations of FAPs in disease development; the role of FAPs in cell-to-cell interactions during skeletal muscle degeneration and regeneration. Current research has outlined how different physiological and pathological conditions alter FAPs’ behavior, highlighting FAPs as a potential target for clinical protocols aimed at treating or mitigating skeletal muscle disorders. Future studies should clarify how FAPs govern cell-to-cell interactions during skeletal muscle degeneration and regeneration, offering critical insights for therapies targeting diverse neuromuscular diseases. Full article

Interleukin-6 (IL-6) is a cytokine with multiple biological effects. It plays a complex and seemingly paradoxical central role in both the physiological homeostasis and pathological processes of skeletal muscle. Under physiological conditions, particularly during acute exercise, IL-6 produced and secreted by the contracting skeletal muscle itself acts as an important “myokine.” It operates in an autocrine, paracrine, or endocrine manner to regulate systemic energy metabolism, insulin sensitivity, muscle regeneration, and adaptive hypertrophy. This function is crucial for the health benefits conferred by exercise. However, under various pathological conditions—such as cancer cachexia, sepsis, muscular dystrophy, denervation, disuse atrophy, and chronic inflammatory diseases—persistently elevated systemic or local IL-6 levels become a key mediator driving skeletal muscle atrophy, metabolic disorders, and functional decline. This review systematically elaborates on the dual role of IL-6 in skeletal muscle. It provides an in-depth analysis of its downstream signaling pathways (e.g., JAK/STAT, gp130, MAPK, PI3K-Akt) and upstream regulatory mechanisms (e.g., the Piezo1/KLF15 axis, calcium signaling, mitochondrial function, oxidative stress). A particular focus is placed on discussing the distinct biological effects of classical IL-6 signaling versus trans-signaling. Furthermore, we address current challenges in research and practice, including the cell specificity of IL-6 signaling, the complexity of its temporal regulation, the definition of physiological versus pathological concentrations, discrepancies between animal models and human diseases, and the plasticity of its function across different pathological contexts. Finally, this review explores the potential of targeting the IL-6 signaling pathway as a therapeutic strategy for skeletal muscle atrophy and related metabolic diseases. Potential interventions include IL-6/IL-6R monoclonal antibodies, JAK/STAT inhibitors, gp130 modulators, exercise interventions, and nutritional strategies. This aims to provide a theoretical foundation and novel perspectives for future translational research and clinical interventions. Full article

Background/Objectives: We report a case of severe dermatomyositis demonstrating characteristic widespread extraosseous uptake on ^99mTc-methylene diphosphonate (^99mTc-MDP) bone scintigraphy. This study highlights the diagnostic value of this modality in detecting active inflammatory myopathy when conventional muscle biopsy is inconclusive and introduces its novel use for intraoperative gamma-probe-guided biopsy to precisely target metabolically active muscle. This approach may help target metabolically active muscle in heterogeneous idiopathic inflammatory myopathies (IIMs). Case Presentation: A 49-year-old man developed progressive proximal muscle weakness (Medical Research Council grade 2/5 proximally, 5/5 distally) beginning in June 2025 following influenza infection, accompanied by dysphagia, classic dermatomyositis cutaneous manifestations, back pain, and difficulty standing. Laboratory evaluation revealed elevated inflammatory markers (ESR 55 mm/hr, CRP 20 mg/L), leukocytosis (16.58 × 10⁹/L), markedly raised creatine kinase (19,937 IU/L), and troponin T levels. An initial quadriceps muscle biopsy performed on 29 July 2025 was non-diagnostic. Three-phase ^99mTc-MDP scintigraphy (~1110 MBq) demonstrated intense, diffuse extraosseous uptake involving bilateral deltoids (symmetric), biceps and triceps (patchy), paraspinal muscles (longitudinal), gluteal muscles, thighs (quadriceps and hamstrings), and gastrocnemius muscles, with relative suppression of appendicular skeletal uptake on delayed images due to soft-tissue tracer dominance—findings consistent with severe inflammatory myopathy. Following reinjection (~1100 MBq), intraoperative gamma-probe-guided biopsy targeted areas of highest uptake (left quadriceps femoris and distal triceps brachii; intraoperative counts 1300–1400 versus background ~500). Histopathology revealed histiocyte-predominant inflammation with myofibre necrosis and regeneration, sparse CD4⁺ T-cell infiltrates, and absence of fibrosis, consistent with necrotising myopathy. Positive antinuclear antibodies and strong anti-Mi-2 antibodies confirmed the diagnosis of dermatomyositis. Treatment included pulse methylprednisolone followed by oral prednisone taper, methotrexate, azathioprine, intravenous immunoglobulin, and planned rituximab therapy. Discussion: Whole-body ^99mTc-MDP scintigraphy provided a complementary whole-body functional assessment of disease extent, revealing widespread muscular involvement. The novel application of intraoperative gamma-probe-guided biopsy enabled real-time targeting of metabolically active muscle, facilitating targeted sampling after an initial non-diagnostic biopsy and yielding supportive histopathological findings. This dual diagnostic and interventional role demonstrates the technical feasibility of gamma-probe guidance in a diagnostically challenging case of dermatomyositis. Conclusions: In our case, the integration of ^99mTc-MDP scintigraphy with gamma-probe-guided biopsy enabled precise targeting of metabolically active muscle following an initial non-diagnostic biopsy. This multimodal approach may be useful in selected diagnostically challenging cases of severe inflammatory myopathy. Larger studies are needed to evaluate its reproducibility and added value. Full article

Skeletal muscle satellite cells (SMSCs) are essential for embryonic myogenesis and postnatal muscle regeneration; however, their cellular heterogeneity and transcriptional dynamics during avian development remain largely unexplored. Here, we performed single-cell RNA sequencing (scRNA-seq) on 42,886 cells isolated from goose leg muscles across four embryonic stages (E13, E15, E18, and E23), with each stage comprising pooled tissues from four female embryos. Unbiased clustering resolved 22 transcriptionally distinct clusters representing six major cell types—satellite cells, myocytes, fibro-adipogenic progenitors, endothelial cells, immune cells, and Schwann cells—with satellite cells being the most abundant. Satellite cells were further subdivided into three functional states (quiescent, activated, and proliferative/differentiating), which followed a continuous, linear pseudotime trajectory from early to late embryonic stages. This trajectory was marked by a progressive downregulation of stemness-associated regulators (e.g., PAX7) and upregulation of myogenic commitment and differentiation factors (e.g., MYF5, MYOD1, and MYOG), faithfully mirroring chronological development. Cell–cell communication analysis revealed that quiescent satellite cells exhibited the most extensive intercellular signaling networks (e.g., FGFR, Ephrin, collagen, CADM), whereas activated and proliferative/differentiating cells showed progressively diminished communication capacity. Across developmental stages, the contribution intensities of key signaling pathways—including SEMA6, CDH, FGF, LAMININ, MK, MPZ, CADM, FN1, and COLLAGEN—varied significantly among satellite cell states, indicating state-specific responsiveness to microenvironmental cues. Collectively, these findings demonstrate that satellite cells dynamically coordinate extrinsic signal integration with intrinsic differentiation programs to achieve orderly myogenic progression. This study provides a high-resolution single-cell atlas of goose SMSC development, uncovering subpopulation heterogeneity, state-specific molecular signatures, and key signaling pathways, with important implications for avian muscle biology and genetic improvement of poultry. Full article

Leukemia inhibitory factor (LIF), a member of the interleukin-6 (IL-6) cytokine family, is a well-characterized myokine with pleiotropic regulatory effects on skeletal muscle. LIF modulates several fundamental cellular processes, including myoblast proliferation, apoptosis, angiogenesis, and energy metabolism. Exercise upregulates LIF expression in skeletal muscle, thereby promoting satellite cell activation, proliferation, myoblast differentiation, and angiogenesis, facilitating physiological muscle hypertrophy, and suppressing myocyte apoptosis and muscle atrophy. In addition, LIF plays a critical role in modulating the inflammatory and extracellular matrix remodeling following exercise-induced muscle damage, thereby supporting efficient muscle repair and regeneration. This review elaborates on the biological mechanisms by which LIF regulates skeletal muscle atrophy and contributes to the enhancement of skeletal muscle function. It also highlights the biological characteristics of myogenic LIF and discusses future directions for basic and applied research on exercise interventions targeting LIF signaling pathways. Full article

Skeletal muscle loss resulting from traumatic injury, sarcopenia, and myopathies remains a major clinical challenge due to the limited regenerative capacity of adult muscle tissue. This review systematically examines advanced biomedical therapeutic approaches to restoring muscle mass and function, including gene therapy, microRNA, cell-based strategies, and tissue engineering. Key mechanisms of muscle histogenesis and regeneration are discussed, with emphasis on the roles of satellite cells, growth factors (IGF-1, VEGF), and transcriptional regulators. Preclinical studies demonstrate that viral and non-viral delivery of myogenic factors can enhance muscle repair, reduce fibrosis, and improve functional outcomes. However, translation to clinical practice is hindered by challenges such as immune responses, inadequate reinnervation, and the complexity of replicating native tissue architecture. Emerging strategies combining gene delivery with rehabilitation, immunomodulation, or exosome therapy show synergistic effects. Although clinical trials targeting sarcopenia and muscle defects using anti-myostatin antibodies, stem cell-derived products, and acellular scaffolds have reported modest gains in strength and lean mass, no definitive regenerative therapy has been approved. While significant progress has been made, achieving full structural and functional muscle regeneration will require combinatorial approaches that address vascularization, innervation, and the inflammatory microenvironment. Full article

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in mammalian skeletal muscle development, moving beyond their initial characterization as transcriptional “noise”. Unlike previous reviews that focus primarily on individual IncRNA catalogues, this review systematically integrates recent advances across five dimensions: (1) molecular characteristics and multidimensional classification of muscle related lncRNAs; (2) stage-specific expression patterns spanning embryonic myogenesis, postnatal growth, adult maintenance, and regeneration; (3) underlying molecular mechanisms including chromatin remodeling, ceRNA networks, IncRNA protein interactions, and nucleocytoplasmic trafficking; (4) pathological implications in muscular dystrophy, atrophy, and neuromuscular diseases; (5) translational applications in precision animal breeding. We critically evaluate the controversial ceRNA hypothesis and highlight quantitative limitations in current evidence. By integrating existing knowledge into a multi-layer regulatory network model and addressing current technical challenges and controversies (e.g., the ceRNA stoichiometry debate), this review provides a comprehensive roadmap for future basic research and translational applications in muscle biology. Full article

Skeletal muscle satellite cells are indispensable for muscle growth and regeneration, and their myogenic differentiation is precisely controlled by transcription factors. As a core member of the TEAD family, TEAD4 participates in various biological processes, yet its function and regulatory mechanism in porcine skeletal muscle satellite cells (PSCs) remain largely unknown. High-purity PSCs were isolated and identified from 7-day-old Large White piglets. Combined approaches of siRNA-mediated TEAD4 knockdown, RT-qPCR, Western blotting, immunofluorescence, EdU assays, and transcriptome sequencing were applied to explore the role of TEAD4 during myogenic differentiation. TEAD4 expression was gradually upregulated during PSC differentiation and positively correlated with myogenic marker genes. Knockdown of TEAD4 did not affect PSC proliferation but significantly suppressed myogenic differentiation, as indicated by reduced expression of myogenic genes and blocked myotube formation. Transcriptomic analysis demonstrated that DEGs were highly enriched in metabolic pathways, particularly the AMPK signaling pathway. TEAD4 knockdown led to excessive upregulation of PRKAG3 and prominent induction of SLC2A4. Collectively, these results indicate that TEAD4 promotes myogenic differentiation in PSCs, likely by maintaining metabolic homeostasis. This study provides the first characterization of TEAD4 in porcine skeletal muscle satellite cells and demonstrates that it promotes myogenic differentiation. Full article

Accumulating evidence suggests that vitamin B6 (B6) deficiency among older adults is associated with sarcopenia, frailty, heart disease, and brain diseases. Oxidative stress and inflammation play key roles in cardiac and skeletal muscle and neuronal pathology. However, the detailed roles of B6 supplementation in oxidative stress and inflammation are not fully understood. Recent studies have shown that supplemental B6 upregulated the nuclear factor erythroid 2-like 2 (Nrf2) signaling pathway with the coordinated activation of antioxidant responses. Accumulating evidence suggests the potential of targeted Nrf2 signaling regulation in the treatment of aging-related musculoskeletal, heart, and brain diseases. Notably, dietary supplementation of B6 elevates the levels of several antioxidant metabolites, such as carnosine, anserine, taurine, hydrogen sulfide (H₂S), 5-methyltetrahydrofolate, kynurenic acid, 3-hydroxyanthranilic acid, and γ-aminobutyric acid (GABA) via the upregulation of pyridoxal 5′-phosphate (PLP)-dependent metabolic pathways, thereby linking to Nrf2 signaling activation. Furthermore, supplemental B6 stimulates glycogen breakdown through the PLP enzyme, glycogen phosphorylase, which in turn enhances the pentose phosphate pathway, thereby increasing nicotinamide adenine dinucleotide phosphate (NADPH) availability to regenerate glutathione (GSH). In this perspective article, we propose the potential role of B6 as an antioxidant mediated by the PLP-dependent multi-metabolic productions of antioxidant metabolites. Full article

Exposure to high-altitude hypoxia leads to complex physiological and molecular adaptations, particularly in skeletal muscle. MicroRNAs (miRNAs), including muscle-enriched (myomiRNAs) and hypoxia-responsive (hypoxamiRNAs), play critical roles in regulating these responses. We investigated miRNA expression changes in the skeletal muscle of healthy, non-smoking Italian adults (mean age 36.7 ± 12.4 years) participating in the Himalayan expedition “Lobuche Peak—Pyramid Exploration & Physiology” conducted in the Sagaramāthā (Mount Everest) National Park, Nepal. The peak overnight stay altitude was ≈5000 m at the Pyramid International Laboratory—Observatory. Muscle biopsies were taken before and after the expedition from Vastus lateralis, at one-third of the distance from the upper margin of the rotula to the anterior superior iliac spine. Small RNA sequencing was used to profile differentially expressed miRNAs. Several miRNAs were differentially expressed (exploratory analysis), suggesting potential involvement in hypoxia-related adaptation. These encompass both canonical myomiRNAs (e.g., miR-206, miR-486-5p) and hypoxamiRNAs (e.g., miR-378a-5p, miR-199a-3p, let-7b-5p). In enrichment analysis, we found several connections between miRNAs and pathways that may play a role in physiological regeneration or differentiation in muscle cells. Among functions, focal adhesion (p-value = 0.001), regulation of actin cytoskeleton (p-value = 0.026), Rap-1 (p-value = 0.007), cAMP (p-value = 0.017), MAPK (p-value = 0.019), and Hippo (p-value = <0.001) signaling pathways were predicted to be the most targeted. These findings provide preliminary insights into physiological adaptation, requiring confirmation in larger and controlled cohorts. Full article

Aging is characterized by progressive degeneration of neuromuscular junctions (NMJs), which significantly contributes to muscle weakness and the development of sarcopenia. Photobiomodulation (PBM), a non-invasive therapeutic method based on the use of low-intensity light, has shown promising results in mitigating muscle degeneration in both experimental and clinical studies. The aim of this study was to evaluate the ultrastructural effects of photobiomodulation on neuromuscular junctions and skeletal muscle fibers in the m. vastus lateralis muscle of aged rats using light and transmission electron microscopy. Male Wistar rats (18 months old, body weight 650–800 g, n = 10) were subjected to photobiomodulation of the right m. vastus lateralis muscle (650 nm, 6 J/cm², four consecutive daily sessions of 3 min each). The contralateral left limb served as an untreated control. Muscle samples were analyzed by light and transmission electron microscopy. Histological examination revealed typical age-related changes in control muscles, including variability in muscle fiber diameter, centrally located nuclei, and an increased volume of connective tissue. Ultrastructural analysis confirmed signs of skeletal muscle aging, such as myofibril fragmentation, sarcomere disorganization, lipofuscin accumulation, and tubular aggregate formation. Morphometric analysis of neuromuscular junctions after photobiomodulation showed an increase in the number of active zones on the presynaptic membrane, elongation of the postsynaptic membrane, and a reduction in the width of the synaptic cleft. In addition, mitochondrial hyperplasia was observed in presynaptic terminals, while the total number of synaptic vesicles decreased. These findings indicate a compensatory reorganization of neuromuscular junctions and suggest that photobiomodulation can enhance their functional activity in aged skeletal muscle. Full article

Heterotopic ossification (HO), the pathological formation of mature bone in non-skeletal soft tissues (e.g., muscles, tendons), severely impairs patient mobility and quality of life. Despite decades of research, systematic analysis of signaling networks across HO subtypes (acquired traumatic HO, hereditary Fibrodysplasia Ossificans Progressiva (FOP), Progressive Osseous Heteroplasia (POH)) remains insufficient, and clinical therapies suffer from high recurrence and severe side effects. This review synthesizes recent advances in HO pathogenesis: FOP involves gain-of-function activin A receptor type I (ACVR1) mutations (mostly R206H), disrupting bone morphogenetic protein (BMP)/Activin A signaling; POH arises from paternal guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) loss-of-function mutations, derepressing Hedgehog signaling via reduced cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) activity; tHO features trauma-induced inflammation/hypoxia activating BMP/transforming growth factor–beta (TGF-β) pathways. Key signaling crosstalk (e.g., BMP-Yes-associated protein (YAP)-Indian hedgehog (IHH)) is integrated, and novel therapies (ACVR1 inhibitors, Activin A antibodies, retinoic acid receptor gamma (RARγ) agonists, adeno-associated virus (AAV)-mediated ACVR1 silencing) are highlighted, with emphasis on subtype-specific efficacy. A stratified, mechanism-based HO management framework is proposed, aiming to accelerate precision therapy development and advance understanding of aberrant tissue regeneration. Full article

Background: Aging is accompanied by a progressive decline in skeletal muscle regeneration, largely due to impaired myogenic differentiation. The proprotein convertase FURIN is a key protease responsible for activating several signaling molecules, including precursors of NOTCH receptors, which regulate cell fate and differentiation. In this study, we investigated whether age-associated downregulation of FURIN contributes to impaired NOTCH2/3 signaling and myogenic function. Methods: An initial bioinformatics analysis of public scRNA-seq data from Genotype-Tissue Expression (GTEx) project indicated age-related expression of genes in the NOTCH signaling pathway. In vitro verification used early- and late-passage C2C12 myoblasts as a model of muscle cell aging to compare the expression of these genes. Late-passage C2C12 cells were transiently transfected with FURIN plasmid to assess restoration of differentiation potential, quantified by the fusion index, myogenic marker expression, and morphology. Results: Expression of FURIN, NOTCH2 and NOTCH3 was negatively correlated with age, whereas GZMB increased with age in GTEx dataset. Late-passage myoblasts exhibited impaired myotube formation, reflecting age-associated loss of myogenic capacity. Restoration of FURIN expression in aged myoblasts was associated with reduced GZMB levels, increased expression of embryonic myosin heavy chain IGF1, and partial recovery of myogenic differentiation and myotube formation. Conclusions: These findings suggest that age-associated loss of FURIN contributes to impaired NOTCH2/3 pathways and myogenic dysfunction. Overexpression of FURIN partially rescues the myogenic phenotype and increases expression of early myogenic markers in aged cells, identifying FURIN as a potential regulator of muscle regenerative capacity during aging. We suggest FURIN as a promising candidate target for further investigation into the mechanisms driving aging or age-related decline. Full article

Different types of skeletal muscle fibers display marked heterogeneity in metabolic, mechanical, and regenerative properties. However, their role in chronic musculoskeletal pain remains insufficiently integrated into clinical models. Chronic pain is associated with altered neuromuscular control, prolonged low-level activation, and reduced recruitment of high-threshold motor units. These factors may promote fiber type-specific remodeling. This narrative review critically synthesizes current evidence on the relationship between musculoskeletal pain and muscle fiber types. The focus was on metabolic vulnerability, mechanical susceptibility, and regenerative capacity. A structured literature search was conducted in PubMed, Scopus, and Web of Science, focused on human studies and key translational models. Chronic musculoskeletal pain is characterized by acquired fiber type-specific adaptations rather than a fixed unfavorable profile. In chronic pain scenarios, Type I fibers present features of chronic overload, including hypertrophy with insufficient capillarization and increased satellite cell activity. Type II fibers exhibit relative disuse, atrophy, and reduced satellite cell content, resembling accelerated muscle aging. Symptom duration, neuromuscular control strategies, and task-specific loading patterns modulate these adaptations, with interindividual variation. Muscle dysfunction in chronic pain reflects maladaptive but potentially reversible neuromuscular and histological plasticity. These findings indicate that rehabilitation strategies should be individualized, involving context-specific exercise strategies to restore muscle structure, function, and regenerative potential in chronic musculoskeletal conditions. Full article