Search Results (42)

Background and Objectives: Vascular calcification (VC) is a major contributor to cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), particularly those on hemodialysis. Once considered a passive process, VC is now recognized as an active, cell-mediated pathology influenced by mineral dysregulation, chronic inflammation, and oxidative stress. This review aims to synthesize current evidence on the underlying mechanisms of VC in CKD and hemodialysis, with particular focus on emerging biomarkers and therapeutic implications. Materials and Methods: A structured narrative review was conducted by searching PubMed, Web of Science, ScienceDirect, and Google Scholar. The final search was completed on 29 August 2025. A total of 1326 articles were initially retrieved, of which 65 met the inclusion criteria and were analyzed. Studies addressing VC mechanisms, the bone–vascular axis, mineral metabolism, vitamin K–dependent proteins, and biomarkers such as matrix Gla protein (MGP), osteocalcin (OC), and intact parathyroid hormone (iPTH) were included. Results: VC in CKD arises from phenotypic transformation of vascular smooth muscle cells, vesicle-mediated calcification, oxidative stress, and impaired activity of endogenous calcification inhibitors. Disruption of the fibroblast growth factor 23 (FGF23)–Klotho axis and secondary hyperparathyroidism further exacerbate vascular pathology. Among emerging biomarkers, dp-ucMGP reflects vitamin K deficiency and correlates with calcification burden, while OC and iPTH provide insight into bone–vascular crosstalk and mineral turnover. However, biomarker interpretation is limited by assay variability, renal clearance, and clinical heterogeneity. Conclusions: VC in CKD represents a complex process driven by systemic and cellular dysregulation. While biomarkers such as dp-ucMGP, OC, and iPTH offer mechanistic insights and prognostic potential, further validation is required for clinical application. A multimarker approach, combined with individualized management of mineral metabolism, may improve risk stratification and therapeutic targeting in this high-risk population. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic condition with a complex pathophysiology involving multiple organs. Organokines, including hepatokines, myokines, cardiokines, renokines, osteokines, and adipokines, play central roles in lipid metabolism, glucose homeostasis, inflammation, and fibrosis. Dysregulation of these signaling molecules contributes to the progression of MASLD and its systemic complications. This review examines the role of organokine-mediated crosstalk between the liver and peripheral organs (e.g., muscle, heart, kidneys, bone, and adipose tissue) in the pathogenesis of MASLD. Key molecules, such as myostatin, FGF-21, IL-6, and adiponectin, influence insulin sensitivity, lipid metabolism, and inflammation. Some organokines have protective effects (e.g., FGF-21, irisin, and klotho), while others, such as myostatin and fetuin-A, exacerbate insulin resistance and fibrosis. These findings suggest that targeting organokines could provide potential biomarkers and therapeutic strategies for MASLD. Future research should focus on elucidating the molecular mechanisms and assessing the role of organokines in the prevention and treatment of MASLD. Full article

Skeletal muscle is increasingly recognized as a dynamic endocrine organ whose secretome—particularly myokines—serves as a central hub for the coordination of systemic metabolic health, inflammation, and tissue adaptation. This review integrates molecular, cellular, and physiological evidence to elucidate how myokine signaling translates mechanical and metabolic stimuli from exercise into biochemical pathways that regulate glucose homeostasis, lipid oxidation, mitochondrial function, and immune modulation. We detail the duality and context-dependence of cytokine and myokine actions, emphasizing the roles of key mediators such as IL-6, irisin, SPARC, FGF21, and BAIBA in orchestrating cross-talk between muscle, adipose tissue, pancreas, liver, bone, and brain. Distinctions between resistance and endurance training are explored, highlighting how each modality shapes the myokine milieu and downstream metabolic outcomes through differential activation of AMPK, mTOR, and PGC-1α axes. The review further addresses the hormetic role of reactive oxygen species, the importance of satellite cell dynamics, and the interplay between anabolic and catabolic signaling in muscle quality control and longevity. We discuss the clinical implications of these findings for metabolic syndrome, sarcopenia, and age-related disease, and propose that the remarkable plasticity of skeletal muscle and its secretome offers a powerful, multifaceted target for lifestyle interventions and future therapeutic strategies. An original infographic is presented to visually synthesize the complex network of myokine-mediated muscle–organ interactions underpinning exercise-induced metabolic health. Full article

Pediatric type 1 diabetes (T1D) disrupts musculoskeletal development during critical windows of growth, puberty, and peak bone mass accrual. Beyond classic micro- and macrovascular complications, accumulating evidence shows a dual burden of diabetic bone disease—reduced bone mineral density, microarchitectural deterioration, and higher fracture risk—and diabetic myopathy, characterized by loss of muscle mass, diminished strength, and metabolic dysfunction. Mechanistically, chronic hyperglycemia, absolute or functional insulin deficiency, and glycemic variability converge to suppress PI3K–AKT–mTOR signaling, activate FoxO-driven atrogenes (atrogin-1, MuRF1), and impair satellite-cell biology; advanced glycation end-products (AGEs) and RAGE signaling stiffen extracellular matrix and promote low-grade inflammation (IL-6, TNF-α/IKK/NF-κB), while oxidative stress and mitochondrial dysfunction further compromise the bone–muscle unit. In vitro, ex vivo, and human studies consistently link these pathways to lower BMD and trabecular/cortical quality, reduced muscle performance, and increased fractures—associations magnified by poor metabolic control and longer disease duration. Prevention prioritizes tight, stable glycemia, daily physical activity with weight-bearing and progressive resistance training, and optimized nutrition (adequate protein, calcium, vitamin D). Treatment is individualized: supervised exercise-based rehabilitation (including neuromuscular and flexibility training) is the cornerstone of skeletal muscle health. This review provides a comprehensive analysis of the mechanisms underlying the impact of type 1 diabetes on musculoskeletal system. It critically appraises evidence from in vitro studies, animal models, and clinical research in children, it also explores the effects of prevention and treatment. Full article

Background: The craniofacial region is functionally unique, with close interaction between muscles and bones during mastication, speech, and facial expression. Although myokines, muscle-derived signaling molecules, are increasingly being studied in relation to bone metabolism, most studies have focused on limb muscles and long bones. Given the developmental and functional specificity of craniofacial structures, this article aims to map the current evidence on myokines involved in craniofacial bone metabolism and to identify gaps in order to guide future research. Methods: We conducted a literature search in PubMed and Scopus (January 2000–July 2025), combining both free-text keywords and MeSH terms to ensure comprehensive retrieval of relevant articles. Results: Nine articles from the extensive search were included in this review that adhered to the eligibility criteria. The myokines that were reported include interleukin-6, insulin like growth factor-1, and myostatin and irisin. Conclusions: Further research is required into the mechanism by which craniofacial muscle-derived myokines regulate local bone metabolism, as this knowledge could pave the way for novel therapeutic strategies that leverage myokine signaling, which could be applied in the context of orthodontic and orthognathic treatments, maxillofacial reconstruction, or age-related bone loss. Full article

Background/Objectives: Obesity and type 2 diabetes mellitus (T2DM) profoundly disrupt lipid metabolism within local microenvironments of skeletal muscle and its associated connective tissues, including adipose tissue, bone, and fascia. However, the role of local communication between skeletal muscle and its proximal connective tissues in propagating metabolic dysfunction is incompletely understood. This narrative review synthesizes current evidence on these local metabolic interactions, highlighting novel insights and existing gaps. Methods: We conducted a comprehensive literature analysis of primary research published in the last decade, sourced from PubMed, Web of Science, and ScienceDirect. Studies were selected for relevance to skeletal muscle, adipose tissue, fascia, and bone lipid metabolism in the context of obesity and T2DM, with emphasis on molecular, cellular, and paracrine mechanisms of local crosstalk. Findings were organized into thematic sections addressing physiological regulation, pathological remodeling, and inter-organ signaling pathways. Results: Our synthesis reveals that local lipid dysregulation in obesity and T2DM involves altered fatty acid transporter dynamics, mitochondrial overload, fibro-adipogenic remodeling, and compartment-specific adipose tissue dysfunction. Crosstalk via myokines, adipokines, osteokines, bioactive lipids, and exosomal miRNAs integrates metabolic responses across these tissues, amplifying insulin resistance and lipotoxic stress. Emerging evidence highlights the underappreciated roles of fascia and marrow adipocytes in regional lipid handling. Conclusions: Collectively, these insights underscore the pivotal role of inter-tissue crosstalk among skeletal muscle, adipose tissue, bone, and fascia in orchestrating lipid-induced insulin resistance, and highlight the need for integrative strategies that target this multicompartmental network to mitigate metabolic dysfunction in obesity and T2DM. Full article

Osteosarcopenia is a widespread geriatric condition resulting from the coexistence of osteoporosis and sarcopenia, where the connection between bone and muscle is, in part, driven by bone–muscle crosstalk. Given the close, reciprocal influence of muscle on nerve, and vice versa, it is not surprising that there are corresponding aging changes in the biochemistry and morphology of the neuromuscular junction (NMJ). Indeed, degeneration of motor neurons and progressive disruption of the neuromuscular connectivity were observed in old age. Extracellular vesicles (EVs) derived from human amniotic fluid stem cells (hAFSC), exhibiting antioxidant properties, which can also explain their anti-aging and cytoprotective effects, can be considered as potential treatment for age-related diseases. To study cell interactions under both healthy and pathological conditions occurring in musculo–skeletal apparatus, we developed a three-culture system exploiting the use of well-known transwell supports. This system allows both myotubes and neurons, eventually treated with EVs, and osteoblasts, induced to osteoporosis, to interact physically and biochemically. Collectively, this method allowed us to understand how the modifications induced in osteoblasts during bone disorders trigger a cascade of detrimental effects in the muscle and neuron parts. Moreover, we demonstrated the efficacy of hAFSC-EVs in preventing NMJ dysfunction, muscle atrophy, and osteoblast impairment. Full article

Osteosarcopenia, characterized by concurrent bone loss and muscle wasting, significantly impacts mobility and quality of life. While age-related primary osteosarcopenia is well-studied, secondary osteosarcopenia (SOS) caused by chronic diseases remains poorly understood, particularly in young individuals. The present study aimed to comprehensively characterize musculoskeletal alterations associated with SOS using a juvenile porcine model of cerulein-induced chronic pancreatitis. Femoral bone analysis included densitometry, mechanical testing, histomorphometry, and serum bone turnover markers. The quadriceps femoris muscle was evaluated through histological analysis and gene expression profiling of antioxidant enzymes and apoptotic regulators. Animals with SOS showed significantly reduced femoral BMD compared to controls, with altered cortical geometry and compromised mechanical properties. Trabecular bone analysis revealed classic osteoporotic changes with decreased bone volume fraction. Negative changes were also observed in the growth plate morphology, indicating impaired endochondral ossification. Bone turnover markers indicated elevated bone resorption and altered formation. Muscle analysis demonstrated sarcopenic changes with selective atrophy of fast-twitch type II fibers and increased fiber density. At the molecular level, SOS muscles exhibited downregulated expression of CAT and CASP3, suggesting muscle atrophy predominantly mediated by oxidative stress and caspase-independent proteolysis rather than classical apoptosis. In conclusion, chronic pancreatitis in young pigs induces coupled bone and muscle degeneration consistent with secondary osteosarcopenia, demonstrating that muscle–bone crosstalk dysfunction occurs early in chronic inflammatory disease. Full article

Skeletal muscles and bones maintain musculoskeletal system function through their collaborative interaction, whereby muscles regulate bone metabolism via mechanical coupling. An increasing number of studies have shown that various cytokines secreted by skeletal muscles during exercise closely regulate the balance of bone homeostasis. Interleukin-6 (IL-6), one of the first muscle-secreted factors to be discovered, not only plays an important role in regulating the function of the muscle itself but also regulates bone metabolic processes in a bidirectional manner through multiple complex signal transduction pathways, thereby affecting the balance between bone formation and bone resorption. The exact mechanism by which IL-6 regulates bone metabolism is not fully understood, and there are few summaries on how exercise affects bone metabolism through IL-6 from skeletal muscles. Accordingly, this study will take skeletal muscle-derived IL-6 as an entry point to explore how the cross-organ regulatory activities of the muscles targeting bones during exercise affect bone metabolic processes. This study also aims to improve the mechanism of muscle–bone crosstalk under the effect of exercise and provide a theoretical basis and clinical diagnosis and treatment ideas from multiple perspectives for exercise to improve bone health. Full article

The importance of dietary calcium intake in bone metabolism has been well established; however, it is still less investigated in health-related components, especially addressing muscle performance. This study aims to compare dietary calcium intake and its relationship with cardiovascular and muscular performance in young athletes (Lacrosse, Baseball, and soccer players). In this cross-sectional study, 95 participants (ages 18 to 30) participated during two visits to the Human Performance Laboratory. Participants completed body composition, lower and upper body muscle performance, cardiorespiratory protocol, and questionnaires related to dietary calcium intake. One-way ANOVA was used to determine the difference in the calcium intake between groups. The Pearson Correlation Coefficient was used to investigate the relationship between dietary calcium intake and muscle performance variables. Further, linear regression was used to assess the predictive value of calcium variables on overall muscle performance. Lacrosse players had significantly higher calcium intake than Baseball and soccer players (p < 0.05). There was a significant positive correlation between dietary calcium intake and the number of push-ups (r = 0.28; p = 0.03). CIBW and CI explained 4.3% and nearly 25% of the change in MPI, respectively (p < 0.001). This suggests the possible role of dietary calcium intake in enhancing health-related fitness components and highlights the need to explore its involvement in muscle-bone crosstalk. Full article

Skeletal muscle plays a crucial role in movement, metabolism, and energy homeostasis. As the most metabolically active endocrine organ in the body, it has recently attracted widespread attention. Skeletal muscle possesses the ability to release adipocytokines, bioactive peptides, small molecular metabolites, nucleotides, and other myogenic cell factors; some of which have been shown to be encapsulated within small vesicles, particularly exosomes. These skeletal muscle exosomes (SKM-Exos) are released into the bloodstream and subsequently interact with receptor cell membranes to modulate the physiological and pathological characteristics of various tissues. Therefore, SKM-Exos may facilitate diverse interactions between skeletal muscle and other tissues while also serving as biomarkers that reflect the physiological and pathological states of muscle function. This review delves into the pivotal role and intricate molecular mechanisms of SKM-Exos and its derived miRNAs in the maturation and rejuvenation of skeletal muscle, along with their intercellular signaling dynamics and physiological significance in interfacing with other tissues. Full article

Galectin-3 (Gal-3) is a pleiotropic lectin produced by most cell types, which regulates multiple cellular processes in various tissues. In bone, depending on its cellular localization, Gal-3 has a dual and opposite role. If, on the one hand, intracellular Gal-3 promotes bone formation, on the other, its circulating form affects bone remodeling, antagonizing osteoblast differentiation and increasing osteoclast activity. From an analysis of the secretome of cultured differentiating myoblasts, we interestingly found the presence of Gal-3. After that, we confirmed that Gal-3 was expressed and released in the extracellular environment from myoblast cells during their differentiation into myotubes, as well as after mechanical strain. An in vivo analysis revealed that Gal-3 was triggered by trained exercise and was specifically produced by fast muscle fibers. Speculating a role for this peptide in the muscle-to-bone cross talk, a direct co-culture in vitro system, simultaneously combining media that were obtained from differentiated myoblasts and osteoblast cells, confirmed that Gal-3 is a mediator of osteoblast differentiation. Molecular and proteomic analyses revealed that the secreted Gal-3 modulated the biochemical processes occurring in the early phases of bone formation, in particular impairing the activity of the STAT3 and PDK1/Akt signaling pathways and, at the same time, triggering that one of Notch. Circulating Gal-3 also affected the expression of the most common factors involved in osteogenetic processes, including BMP-2, -6, and -7. Intriguingly, Gal-3 was able to interfere with the ability of differentiating osteoblasts to interact with the components of the extracellular bone matrix, a crucial condition required for a proper osteoblast differentiation. All in all, our evidence lays the foundation for further studies to present this lectin as a novel myokine involved in muscle-to-bone crosstalk. Full article

Calcium research, since its pivotal discovery in the early 1800s through the heating of limestone, has led to the identification of its multi-functional roles. These include its functions as a reducing agent in chemical processes, structural properties in shells and bones, and significant role in cells relating to this review: cellular signaling. Calcium signaling involves the movement of calcium ions within or between cells, which can affect the electrochemical gradients between intra- and extracellular membranes, ligand binding, enzyme activity, and other mechanisms that determine cell fate. Calcium signaling in muscle, as elucidated by the sliding filament model, plays a significant role in muscle contraction. However, as organisms age, alterations occur within muscle tissue. These changes include sarcopenia, loss of neuromuscular junctions, and changes in mineral concentration, all of which have implications for calcium’s role. Additionally, a field of study that has gained recent attention, cellular senescence, is associated with aging and disturbed calcium homeostasis, and is thought to affect sarcopenia progression. Changes seen in calcium upon aging may also be influenced by its crosstalk with other minerals such as iron and zinc. This review investigates the role of calcium signaling in aging muscle and cellular senescence. We also aim to elucidate the interactions among calcium, iron, and zinc across various cells and conditions, ultimately deepening our understanding of calcium signaling in muscle aging. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and a major cause of age-related dementia, characterized by cognitive dysfunction and memory impairment. The underlying causes include the accumulation of beta-amyloid protein (Aβ) in the brain, abnormal phosphorylation, and aggregation of tau protein within nerve cells, as well as neuronal damage and death. Currently, there is no cure for AD with drug therapy. Non-pharmacological interventions such as exercise have been widely used to treat AD, but the specific molecular and biological mechanisms are not well understood. In this narrative review, we integrate the biology of AD and summarize the knowledge of the molecular, neural, and physiological mechanisms underlying exercise-induced improvements in AD progression. We discuss various exercise interventions used in AD and show that exercise directly or indirectly affects the brain by regulating crosstalk mechanisms between peripheral organs and the brain, including “bone–brain crosstalk”, “muscle–brain crosstalk”, and “gut–brain crosstalk”. We also summarize the potential role of artificial intelligence and neuroimaging technologies in exercise interventions for AD. We emphasize that moderate-intensity, regular, long-term exercise may improve the progression of Alzheimer’s disease through various molecular and biological pathways, with multimodal exercise providing greater benefits. Through in-depth exploration of the molecular and biological mechanisms and effects of exercise interventions in improving AD progression, this review aims to contribute to the existing knowledge base and provide insights into new therapeutic strategies for managing AD. Full article

The importance of various markers such as Sclerostin, Dickkopf-1 (DKK-1), Irisin, receptor activator of NF-kB ligand (RANKL), and Vitamin D have been well studied in bone metabolism. Additionally, inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and Interleukin 6 (IL-6) have been shown to hinder muscle protein synthesis, leading to the loss of muscle and strength. However, a research gap exists in understanding their role in muscle function and physical activity. Therefore, this study aims to explore the serum levels of Sclerostin, DKK-1, Irisin, IL-6, RANKL, Vitamin D, and TNF-α and assess their relationships with upper- and lower-body strength in young adults. In this study, 38 college-aged students (18–23 years), males and females, participated and completed the protocols. The participants’ lower and upper body strength were assessed by the vertical jump test (Just Jump, Probotic, AL) with a Tendo FitroDyne (Tendo Sports Machines, Trencin, Slovak Republic) and handgrip (HG) dynamometry (Takei Scientific Instruments, Yashiroda, Japan), respectively. Fasting morning blood samples were analyzed for serum levels of biomarkers by ELISA. The results indicate significant sex differences in Sclerostin, DKK-1, Irisin, and Vitamin D levels (p < 0.05). Furthermore, a positive association was observed between Sclerostin, DKK-1, and Vitamin D, with lower body muscle performance variables (p < 0.05). Conversely, a significant negative correlation was observed between TNF-α and lower-body muscle performance variables (p < 0.05). The results suggest that these markers may have a distinct effect on muscle performance, underscoring the need for further investigation to elucidate the concept of muscle–bone crosstalk. Full article