Search Results (2,476)

Metabolic bone disease (MBD) is clinically characterized by bone deformities and is associated with vitamin D3 deficiency in diurnal animals. However, the pathogenesis and etiology of this condition in flying foxes, considered nocturnal animals, are poorly understood. Therefore, we conducted a survey aimed at various zoological parks housing flying foxes to elucidate the pathogenesis and etiology of MBD in these animals. Our results indicate that vitamin D3 may play a role in preventing metabolic bone disease in flying foxes due to its involvement in calcium absorption. However, these nocturnal animals seem to obtain vitamin D3 primarily through dietary sources in contrast to the cutaneous absorption described in diurnal species. Additionally, our results suggest that an appropriate diet for this species, including fruits, green vegetables, and other protein sources such as animal products and mineral supplementation, could contribute to preventing metabolic bone disease. Full article

The circadian clock is a fundamental timekeeping system that regulates rhythmic biological processes in response to environmental light–dark cycles. In mammals, core clock genes (CLOCK, BMAL1, PER, and CRY) orchestrate these rhythms through transcriptional–translational feedback loops, influencing various physiological functions, including bone remodeling. Bone homeostasis relies on the coordinated activities of osteoblasts, osteoclasts, and osteocytes, with increasing evidence highlighting the role of circadian regulation in maintaining skeletal integrity. Disruptions in circadian rhythms are linked to bone disorders such as osteoporosis. Posttranslational modifications (PTMs), including phosphorylation, acetylation, and ubiquitination, serve as crucial regulators of both circadian mechanisms and bone metabolism. However, the specific role of PTMs in integrating circadian timing with bone remodeling remains underexplored. This review examines the intersection of circadian regulation and PTMs in bone biology, elucidating their impact on bone cell function and homeostasis. Understanding these interactions may uncover novel therapeutic targets for skeletal diseases associated with circadian disruptions. Full article

An Mg-based alloy device manufactured via a superplastic forming process (Mg-AZ31+SPF) and coated using a hydrothermal method (Mg AZ31+SPF+HT) was investigated as a method to increase mechanical and osteointegration capability. The cell viability and osteointegrative properties of alloy-derived Mg AZ31+SPF and Mg AZ31+SPF+HT extracts were investigated regarding their effect on human mesenchymal stem cells (hMSCs) (maintained in basal (BM) and osteogenic medium (OM)) after 7 and 14 days of treatment. The viability was analyzed through metabolic activity and double-strand DNA quantification, while the osteoinductive effects were evaluated through qRT-PCR, osteoimage, and BioPlex investigations. Finally, a preliminary liquid mass spectrometry analysis was conducted on the secretome of hMSCs. Biocompatibility analysis revealed no toxic effect on cells’ viability or proliferation during the experimental period. A modulation effect was observed on the osteoblast pre-commitment genes of hMSCs treated with Mg-AZ31+SPF+HT in OM, which was supported by mineralization nodule analysis. A preliminary mass spectrometry investigation highlighted the modulation of protein clusters involved in extracellular exosomes, Hippo, and the lipid metabolism process. In conclusion, our results revealed that the Mg AZ31+SPF+HT extracts can modulate the canonical and non-canonical osteogenic process in vitro, suggesting their possible application in bone tissue engineering. Full article

Background: High-altitude hypoxia is known to adversely affect bone health, leading to accelerated bone loss and metabolic alterations. Recent studies suggest that factors such as bicarbonate and gut microbiota may play key roles in bone health. Mineral water, rich in bicarbonate, may influence bone health and the gut–bone axis under such conditions. Methods: Mice were exposed to hypoxia and treated with different concentrations of drinking water. Bone-related parameters were assessed using dual-energy X-ray absorptiometry (DXA) and Micro-CT. Bone health was assessed using the measurement of serum biomarkers. Additionally, Untargeted Metabolomics was employed to analyze differential metabolites between groups, while gut microbiota composition was analyzed using 16S rRNA sequencing. Results: BMW consumption increased bone mineral density (BMD) and helped alleviate the damage to the microstructure of bones caused by hypoxia and delayed the progression of osteoporosis. Additionally, BMW was shown to enhance probiotics such as Akkermansia and Dubosiella and regulate the longevity-regulating pathway as well as the PI3K/AKT/mTOR (PAM) signaling pathway. This study also discovered changes in metabolic products due to BMW intervention, predominantly in pathways such as the amino acid, prostaglandin, and purine metabolisms, with correlation analysis further exploring the relationships between gut microbiota and these differential metabolites. Conclusions: Long-term exposure to high-altitude hypoxic conditions affects the structure of gut microbiota and bone metabolism in mice. The consumption of BMW improves the structure of gut microbiota and regulates the metabolic pathways to maintain bone health under high-altitude hypoxia. Full article

Antioxidant peptides are a well-known functional food exhibiting multiple biological activities in health and disease. This study investigated the effects of three peptides, LR-7 (LALFVPR), KA-8 (KLHDEEVA), and PG-7 (PSRILYG), from Harpadon nehereus bone on sodium palmitate (PANa)-induced HepG2. The findings indicated that all three peptides significantly reduced the oxidative damage and fat accumulation in the HepG2 cells while also normalizing the abnormal blood lipid levels caused by PANa. Furthermore, treatment with LR-7 resulted in a more than 100% increase in catalase (CAT), glutathione peroxidase (GSH-Px), and nuclear factor erythroid 2-related factor 2 (Nrf2) levels within the HepG2 cells (p < 0.001). Western blot analysis showed that LR-7 treatment significantly lowered the expression of fatty acid synthase (FASN) by 59.6% (p < 0.001) while enhancing carnitine palmitoyl transferase 1 (CPT1) by 134.7% (p < 0.001) and adipose triglyceride lipase (ATGL) by 148.1% (p < 0.001). Additionally, these peptides effectively inhibited the pancreatic lipase activity. Notably, LR-7 demonstrated superior effectiveness across all of the evaluated parameters, likely due to its greater hydrophobicity. In summary, LR-7, KA-8, and PG-7 are effective at mitigating oxidative stress as well as regulating lipid metabolism, thus protecting HepG2 cells from PANa-induced injury and lipid buildup. This research indicates that these collagen-derived peptides, especially LR-7, show promise as natural agents for managing hyperlipidemia. Full article

Background: FGF23 is a phosphate homeostasis regulator; the literature suggests a link between FGF23, iron homeostasis and erythropoiesis. Little is known about the FGF23 level variations in β-thalassemia (βT), which is characterized by ineffective erythropoiesis and iron overload. Our cross-sectional study aims to evaluate the iFGF23 level variations in a large cohort of βT patients considering their bone mineral densities (BMDs) and iron loads. Methods: Clinical, biochemical and radiological data were collected from 213 transfusion-dependent βT (TDT) adults referring to the Regional HUB Centre for Thalassaemia and Haemoglobinopathies in Ferrara, Italy. The iFGF23 levels in the TDT patients were compared to the general population’s reference range. The BMDs and hearth and liver iron deposits were assessed with DEXA scans and MRI, respectively. Results: The iFGF23 distribution in the TDT subjects is significantly different from that of the general population. The iFGF23 levels are positively correlated with the age at transfusion initiation and calcium and phosphate levels and are negatively correlated with the osteocalcin plasma levels. Patients treated with deferasirox had lower iFGF23 levels than those treated with other chelators. The iFGF23 levels are not correlated with the BMD or iron status. Conclusions: These findings provide insights into the relationship between the iFGF23 and bone and iron metabolism in TDT patients. Further studies are needed to explore its potential clinical relevance. Full article

Osteoporosis and bone defects are commonly observed in postmenopausal women, often linked to decreased folic acid levels, which play a crucial role in bone metabolism and regeneration. This study investigates 3D-printed polyethylene terephthalate glycol (PETG)-based porous scaffolds impregnated with chitosan (CS), hydroxyapatite (HAp), and folic acid (FA) for bone tissue engineering applications. The PETG-CS scaffold serves as the primary structural framework, with HAp incorporated to enhance bioactivity through its osteoconductive and osteoinductive properties. FA was included to address potential deficiencies in bone quality and to stimulate cellular differentiation. The scaffolds were fabricated using precise 3D printing techniques, yielding structures with controlled porosity. Physicochemical analyses confirmed the successful integration of HAp and FA into the PETG-CS matrix. Biological evaluations using preosteoblast cell lines demonstrated enhanced cell viability, proliferation, and biocompatibility of the scaffolds. These findings highlight the promising applications of PETG-CS-HAp-FA scaffolds in bone tissue engineering, providing a platform for future investigations into personalized regenerative therapies. Full article

Recent advancements in tissue engineering and stem cell science have positioned bone disease treatment as a promising frontier in regenerative medicine. This review explores the hormonal and signaling pathways critical to bone regeneration, with a focus on their clinical relevance. Key endocrine factors, including thyroid hormones (T3 and T4), insulin-like growth factor 1 (IGF-1), bone morphogenetic proteins (BMPs), parathyroid hormone (PTH), calcitonin, and fibroblast growth factor 23 (FGF23), play pivotal roles in bone remodeling by regulating osteoblast activity, bone resorption, and mineralization. These factors primarily act through the Wnt/β-catenin, BMP, and FGF signaling pathways, which govern bone repair and regeneration. While animal models, such as axolotls, zebrafish, and Xenopus laevis, provide valuable findings about these mechanisms, translating these findings into human applications presents challenges. This review underscores the therapeutic potential of modulating these hormonal networks to enhance bone regeneration while cautioning against possible adverse effects, such as uncontrolled tissue proliferation or metabolic imbalances. By integrating knowledge from regenerative models, this work provides a foundation for optimizing hormone-based therapies for clinical applications in bone repair and disease treatment. Full article

Cruciferae family vegetables are remarkably high in phytochemicals such as Indole-3-carbinol (I3C) and Diindolylmethane (DIM), which are widely known as nutritional supplements. I3C and DIM have been studied extensively in different types of cancers like breast, prostate, endometrial, colorectal, gallbladder, hepatic, and cervical, as well as cancers in other tissues. In this review, we summarized the protective effects of I3C and DIM against cardiovascular, neurological, reproductive, metabolic, bone, respiratory, liver, and immune diseases, infections, and drug- and radiation-induced toxicities. Experimental evidence suggests that I3C and DIM offer protection due to their antioxidant, anti-inflammatory, antiapoptotic, immunomodulatory, and xenobiotic properties. Apart from the beneficial effects, the present review also discusses the possible toxicities of I3C and DIM that are reported in various preclinical investigations. So far, most of the reports about I3C and DIM protective effects against various diseases are only from preclinical studies; this emphasizes the dire need for large-scale clinical trials on these phytochemicals against human diseases. Further, in-depth research is required to improve the bioavailability of these two phytochemicals to achieve the desirable protective effects. Overall, our review emphasizes that I3C and DIM may become potential drug candidates for combating dreadful human diseases. Full article

Background/Objectives: Low bone mineral density (BMD) is common in hemophilia patients. Identifying high-risk patients for low BMD early is essential to prevent complications and reduce morbidity. The parathyroid hormone (PTH)/calcium (Ca) ratio is a cost-effective marker for predicting BMD, highlighting the need for routine screening and early intervention in this population. Hemophilia is a hereditary bleeding disorder caused by deficiencies in clotting factors VIII (hemophilia A) and IX (hemophilia B). Patients with hemophilia are at risk of low bone mineral density (BMD). This study aimed to evaluate the prevalence of low BMD, associated risk factors, and raise awareness regarding its significance in hemophilia patients. Methods: We retrospectively assessed bone metabolism in 62 hemophilia patients followed at our center. BMD was evaluated using dual-energy X-ray absorptiometry (DEXA). Additionally, serum levels of 25-OH-D3, alkaline phosphatase, PTH, Ca, phosphor, and creatinine were measured. The PTH/Ca, PTH/25-OH-D3, and Ca×25-OH-D3/PTH ratios were calculated. Results: The median age of the 62 patients with hemophilia included in the study (hemophilia A: 87.1%, hemophilia B: 12.9%) was 37 years (range: 21–66), and all were male. Of these patients, 67.7% (n = 42) had severe, 21% (n = 13) had moderate, and 11.3% (n = 7) had mild hemophilia. A total of 85.5% of patients were on factor prophylaxis, and 75.4% had a target joint. In laboratory analysis, the median 25-OH-D3 level was 13.4 µg/L and 75% patients had 25-OH-D3 deficiency. According to DEXA results, 62.9% had lower than normal BMD. When we divided the patients into normal and low BMD groups according to DEXA results, weight (p = 0.006), height (p = 0.024), factor levels (p = 0.004), PTH (p = 0.010), AST (p = 0.029), and PTH/Ca (p = 0.011) levels were statistically significantly different between the groups. The severity of the disease and the rate of receiving prophylaxis were higher in the group with low BMD (p = 0.015, p = 0.006, respectively). In multivariate analysis, PTH/Ca ratio and weight were found to be independent risk factors for BMD. A linear relationship was found between PTH/Ca ratio and BMD. The optimal cut-off value for PTH/Ca was 6.57, with a selectivity of 65% and specificity of 82%. When we divided the patients into groups according to the cut-off value of 6.57, we found that the probability of low BMD increased approximately 7-fold in the group with PTH/Ca > 6.57 (OR 7.045, 95% CI 1.485–33.42, p = 0.014). There was an inverse association between patient weight and low BMD (p = 0.043). Conclusions: Low BMD is a critical public health concern frequently observed in patients with hemophilia. The study highlights a high rate of low BMD and 25-OH-D3 deficiency in hemophilia patients, with the PTH/Ca ratio shown to be useful in predicting BMD. The PTH/Ca ratio is suggested as an accessible, cost-effective, and practical test for evaluating BMD in hemophilia patients. Full article

Bone metabolism dynamic balance is pivotal to bone formation in broilers. Long photoperiods have resulted in leg bones disorders in broilers. Melatonin (MT) is an essential hormone that protects the growth and development of bones, but the functions of melatonin on leg bone metabolism are poorly defined in long photoperiod broilers. A total of 216 healthy 5-day-old Arbor Acres (AA) male broiler chickens were randomly allocated into three treatment groups, i.e., 12L:12D photoperiod, 18L:6D photoperiod, 18L:6D photoperiod with exogenous MT supplementation (18L:6D + MT) for 2 weeks. Here, we found that 18L:6D photoperiod increased tibial length (p < 0.001), circumference (p = 0.012) and long diameter (p = 0.003) of broilers, but decreased the tibial weight index (p = 0.038) and strength. The 18L:6D photoperiod induced the tibial cartilage damage, decreased the osteoblast/osteoclast ratio (p = 0.002) and decreased the medullary cavity collagen fiber (p = 0.018) in broilers. Exogenous MT improved the tibial strength, relieved the tibial cartilage damage, increased the tibia osteoblast activity, alleviated osteoclast recruitment and activation and enhanced the collagen fiber in medullary cavity in long photoperiod broilers. Taken together, exogenous MT improved the tibial performance, morphology and formation of broilers underlying long photoperiod. Full article

Vitamin D (VD) is a fat-soluble steroid hormone with essential physiological functions beyond calcium and bone metabolism. In recent years, its role in women’s reproductive health has gained attention, influencing ovarian function, follicular development, endometrial receptivity, and steroid hormone regulation. VD deficiency has been linked to reproductive disorders such as polycystic ovarian syndrome (PCOS), endometriosis, and infertility. Studies indicate that up to 40–50% of healthy pregnant women have insufficient VD levels, which may contribute to adverse pregnancy outcomes and reduced fertility. With growing evidence connecting VD to reproductive health, this review examines its molecular and endocrine mechanisms in fertility, endometriosis, and PCOS. It explores VD’s therapeutic potential and its implications for improving clinical approaches and future research in reproductive medicine. Maintaining adequate VD levels is crucial for ovarian function, immune modulation in reproductive tissues, and overall fertility. Its deficiency is associated with insulin resistance, hormonal imbalances, and inflammatory processes, which contribute to reproductive pathophysiology. Establishing reference values for VD in reproductive medicine is essential for optimizing fertility treatments and improving clinical outcomes. This review synthesizes current research on VD’s role in reproductive health and highlights the need for further investigation into its therapeutic applications. Full article

Background: Osteoporosis is frequently observed in patients with chronic pancreatitis, and both conditions are closely associated with systemic metabolic disorders. However, the underlying mechanisms linking chronic pancreatitis and osteoporosis remain unclear. Methods: In this study, we utilized high−performance liquid chromatography–mass spectrometry (HPLC−MS) to conduct metabolomics and lipidomics analyses on pancreatic, serum, and other tissues from a mouse model of chronic pancreatitis−induced osteoporosis (CP−OP), with the aim to elucidate the metabolism−related pathogenic mechanisms of CP−OP. Results: We identified over 405 metabolites and 445 lipids, and our findings revealed that several metabolites involving the tricarboxylic acid (TCA) cycle, as well as triacylglycerols and diacylglycerols with higher saturation, were significantly increased in the CP−OP model. In contrast, triglycerides with higher unsaturation were decreased. Differential pathways were enriched in n−3 long−chain polyunsaturated fatty acid metabolism in both pancreatic and bone tissues, and these pathways exhibited positive correlations with bone−related parameters. Furthermore, the modulation of these polyunsaturated fatty acids by Qingyi granules demonstrated significant therapeutic effects on CP−OP, as validated in mouse models. Conclusions: Through the metabolomics approach, we uncovered that disorders in polyunsaturated fatty acids play a critical role in the pathogenesis of CP−OP. This study not only enhances our understanding of the pathogenesis of CP−OP but also highlights the therapeutic potential of targeting polyunsaturated fatty acids as a future intervention strategy for osteoporosis treatment. Full article

Background/Objectives: Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) is a debilitating condition resulting from impaired bone metabolism and vascular disruption due to prolonged glucocorticoid use. This study aimed to explore the therapeutic potential of salvigenin, a flavonoid with antioxidative and estrogen-like properties, in alleviating GIOFH by modulating estrogen receptor alpha (ESR1) pathways. Methods: A network pharmacology approach was utilized to identify salvigenin’s potential targets and their association with GIOFH. Protein–protein interaction networks, along with Gene Ontology and KEGG pathway analyses, were conducted to clarify salvigenin’s multi-target mechanisms. Molecular docking and dynamics simulations assessed the interaction between salvigenin and ESR1. Experimental validation included in vitro assays on MG63 cells treated with dexamethasone (Dex) to mimic GIOFH, evaluating oxidative stress, apoptosis, osteogenic differentiation, and ESR1 expression. Results: Network analysis identified ESR1, NOS3, and MMP9 as key hub targets of salvigenin. Molecular docking and dynamics simulations confirmed stable binding of salvigenin to ESR1. Salvigenin significantly reduced Dex-induced oxidative stress and apoptosis in osteoblasts while restoring osteogenic differentiation and ESR1 expression. Functional assays showed improved mineralized nodule formation, ALP activity, and mitochondrial integrity in salvigenin-treated cells. Conclusions: Salvigenin exhibits significant therapeutic potential in addressing GIOFH through ESR1-mediated pathways. These results offer a strong foundation for future translational studies and the development of salvigenin-based therapies for glucocorticoid-induced bone disorders. Full article

Factor VIII (FVIII) is involved in several molecular pathways and biological processes; indeed, it has a role in the coagulative cascade, cardiovascular disease, hypertension, brain and renal function, cancer incidence and spread, macrophage polarization, and angiogenesis. Hemophilic patients usually present an increase in fracture risk, bone resorption, and an excess of osteoporosis as compared to healthy individuals. Several studies have tried to clarify their etiology but unfortunately it is still unclear. This review focuses on the role of FVIII in bone biology by summarizing all the knowledge present in the literature. We carried out a systematic review of the available literature following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Several studies demonstrated that FVIII is involved in different molecular pathways interfering with bone physiology; it exerts interesting effects on OPG/RANK/RANKL pathways and thrombin/PAR1 pathways. These data confirm a relationship between FVIII and bone metabolism; however, there are still many aspects to be clarified. This review highlights the role of the coagulation factor FVIII in bone metabolism, suggesting new hypotheses for future studies both in vitro and in vivo to better understand the important pleiotropic role of FVIII and hopefully to develop new therapeutic agents for skeletal diseases. Full article