Search Results (67)

Using colorimetric ELISA, this study aims to assess the impact of Gum Arabica (GA) consumption on functional molecular plasma biomarkers of chronic kidney disease (CKD) via a prospective cohort of GA-consumers (cases) vs. non-consumer (age- and CKD stage-matched) controls. Cohort’s hypertension (92.5%), dyslipidemia (64.8%), and diabetes mellitus (54.8%) were prevalent; the mean CKD duration was 6.94 years (SD 7.8) for both study groups. Comparable eGFR, sCr, ESR, CRP, HbA1c, FPG, UA, and fasting lipid parameters were in both study arms. In consumer cases, the mean duration of GA-consumption was 1.3 ± 1.1 (range 0.25–6) years with a mean dose of 1.7 ± 1.0 (range 0.5–6) spoons per day. Leucine-rich alpha 2-glycoprotein, plasminogen activator inhibitor 1, sirtuin 1, and SOST–sclerostin 1 were significantly (p value < 0.01) of lower concentrations, but lipocalin 2 and uromodulin were invariably (p value < 0.05) greater in the GA-consumer cases than those of controls. Strikingly, cystatin C, myeloperoxidase, orosomucoid 1, and symmetric dimethylarginine lacked any substantial variations in the GA-consumer cases vs. those in controls (p value > 0.05). Proportional correlations of CKD duration–PAI1 levels and sCr-lipocalin 2 levels but inverse correlations of orosomucoid 1-hypertension duration and SDMA-DBP were evident in cases. Full article

Although the clownfish, Amphiprion ocellaris (A. ocellaris), is a popular ornamental marine fish worldwide, the mechanisms underlying color pattern variation remain unclear. Given that the Platinum-type clownfish, nearly entirely white, has high economic value, understanding the biological mechanism that accounts for the difference between orange and white colors in A. ocellaris is crucial. To investigate these coloration differences, we performed RNA sequencing analysis and identified differentially expressed genes (DEGs) by comparing white and orange skin samples from three A. ocellaris individuals. A total of 76 DEGs were detected, including 56 downregulated and 20 upregulated genes. DEG sequences were annotated using Danio rerio and Stegastus partitus as reference species, selecting the best hit based on the lowest E-value. A protein–protein interaction (PPI) network and Gene Ontology biological process terms were additionally analyzed. Several DEGs previously reported to be associated with pigmentation, including hpdb, cldn11b, sfrp5, slc2a9, slc2a11b, si:ch211-256m1.8, fhl2, rab38, and ttc39b were identified. Based on the functions of these DEGs, it is inferred that leucophores and xanthophores contribute to both white and orange coloration by modulating related genes, including slc2a11b and slc2a9. Additionally, sfrp5, sost, and sp7 genes were identified to interact with each other in the PPI analysis, with sfrp5 and sost being associated with the Wnt signaling pathway, which contributes to melanocyte specification and osteoblast differentiation. Based on these findings, we propose sost and sp7 as candidate genes that might provide insights relevant to extreme white pigmentation phenotypes, such as those observed in Platinum-type clownfish. For a clearer understanding, further studies integrating quantitative genetics and functional analyses are required. Full article

Background/Objectives: Changes in sclerostin expression regulated by SOST in osteocytes during spaceflight may be associated with bone loss; however, the underlying mechanisms remain unclear. The aim of this study was to clarify the relationship between SOST expression and bone loss by identifying the gene expression differences between osteocytes with high and low SOST expressions. Methods: We used the NASA GeneLab Database OSD-324, which is a microarray of data about the Ocy454 osteocytic cell line cultured for 2, 4, and 6 days during spaceflight, and the GSE102958 microarray in the Gene Expression Omnibus. We also analyzed the characteristics of SOST gene expression in osteocytes during spaceflight using merged datasets. Results: The findings of Gene Set Enrichment Analysis (GSEA) revealed that five gene sets related with H3K27me3 significantly upregulated with NES > 2.0 during spaceflight compared with ground controls. We also found 77 and 617 differentially expressed genes (DEGs) in flight 6d vs. low and high SOST expression, respectively. We used the transcriptional regulatory relationships unraveled by the sentence-based text-mining (TRRUST) database to determine the most significant upstream transcription factor (TF) of genes downregulated in osteocytes during spaceflight compared with those expressing abundant SOST. We detected that TF Sp7 is the most significant, with FDR < 0.01. Moreover, the GSEA findings indicated that the hypoxic pathway is prolonged in osteocytes during spaceflight compared to those at ground level. Conclusions: The gene expression profiles of osteocytes during spaceflight and in comparatively immature osteocytes with low SOST expression were similar. Furthermore, early osteocyte maturation inhibited by downregulated Sp7 during spaceflight extended the hypoxic response. Full article

Background/Objectives: Sclerostin is a glycoprotein produced by osteocytes that regulates osseous remodeling, particularly in the context of orthodontic tooth movement. The purpose of the current systematic review is to assess the effect of orthodontic tooth movement (OTM) on sclerostin expression (SE) in the alveolar bone matrix (ABM). Methods: Indexed databases including PubMed, Embase and Web of Science were searched without time and language restrictions up to and including March 2025. Results: Seven studies performed on 8- to 12-week-old male rodents were included. The magnitude of orthodontic forces ranged from 10–120 g. Distalization and mesialization of the maxillary first molar were performed in one and six studies, respectively. In two studies, SE was increased on the compression and tension sides during OTM. In one study, SE is increased and decreased on the compression and tension sides, respectively; and another reported no difference in SE on the compression and tension sites during OTM. Two studies did not report data on SE on the control-sites (sites unexposed to OTM). Sample-size estimation was not performed in any of the included studies. All studies had a high risk of bias (RoB) and low certainty of evidence (CoE). Conclusions: Sclerostin may play a regulatory role in ABM during OTM. However, current evidence is limited by methodological inconsistencies, high RoB, and low CoE. Well-designed, power-adjusted studies using standardized protocols are required to establish reproducible findings and assess the translational potential of SE in orthodontics. Full article

Osteocytes translate fluid shear stress into biochemical signals critical for bone homeostasis. Here, we combined 3-dimensional (3D) osteocyte culture, microgravity simulation, fluid shear mimicking reloading after disuse, and real-time calcium signaling analysis to elucidate responses of osteocytes under different mechanical environments. Ocy454 cells were seeded onto 3D scaffolds and cultured under static (control) or simulated microgravity (disuse) conditions using a rotating wall vessel bioreactor. Elevated expression levels of Sost, Tnfsf11 (Rankl), and Dkk1 were detected following disuse, confirming efficacy of the microgravity model. Cell membrane integrity under mechanical challenge was evaluated by subjecting scaffold cultures to fluid shear in medium containing FITC-conjugated dextran (10 kDa). The proportion of dextran-retaining cells, indicative of transient membrane disruption and subsequent repair, was higher in microgravity-exposed osteocytes than controls, suggesting increased susceptibility to membrane damage upon reloading following disuse. Intracellular calcium signaling was assessed under a high but physiological fluid shear stress (30 dynes/cm²). Scaffolds cultured under disuse conditions demonstrated a larger sub-population of osteocytes with high calcium signaling intensity (F/Fo > 10 fold) during fluid shear. The maximum fold change in calcium signaling intensity over baseline and the duration of the peak calcium wave were greater for osteocytes cultured under disuse as compared to static controls, however the bioreactor-cultured osteocytes showed, on average, fewer calcium waves than those cultured under control conditions. Subsequent experiments demonstrated that the sub-population of osteocytes with high calcium signaling intensity following exposure to disuse were those that had experienced a transient membrane disruption event during reloading. Together, these results suggest that simulated microgravity enhances osteocyte susceptibility to formation of transient membrane damage and alters intracellular calcium signaling responses upon reloading. This integrated approach establishes a novel platform for mechanistic studies of osteocyte biology and could inform therapeutic strategies targeting skeletal disorders related to altered mechanical loading. Full article

The bone and brain, though distinct in structure and function, share remarkable physical, molecular, and developmental similarities. Emerging evidence reveals dynamic bidirectional crosstalk between these systems mediated by hormones, cytokines, extracellular vesicles (EVs), and neural signals. Bone-derived factors such as osteocalcin (OCN), lipocalin-2, and fibroblast growth factor (FGF) 23 influence cognitive functions, mood, and neurogenesis, while brain- and nerve-derived mediators, including leptin, serotonin, and sympathetic signals, modulate bone remodeling. Inflammation and aging disrupt this communication, contributing to cognitive decline, osteoporosis, and other age-related disorders. Stem cells and EVs have also been implicated as mediators in this axis, offering insights into regenerative strategies. Molecular signaling pathways and transcriptional regulators, such as Wnt/β-catenin, leptin, receptor activator of nuclear factor kappa-B ligand (RANKL), sclerostin (SOST), and nuclear factor kappa-B (NF-κB), play critical roles in maintaining bone–brain homeostasis. Additionally, shared biomarkers and pathological links between neurodegeneration and bone loss suggest new diagnostic and therapeutic opportunities. Studies support this inter-organ communication, yet further mechanistic and translational research is needed. This review highlights the molecular basis of bone–brain crosstalk, emphasizing inflammation, aging, and regulatory pathways, with a focus on future directions in biomarker discovery and therapeutic targeting. Understanding this crosstalk may help in early diagnosis and dual-targeted interventions for both bone and brain disorders. Full article

Background: Ankylosing spondylitis (AS) is a chronic autoinflammatory rheumatic disease mainly affecting the sacroiliac joints and spine, causing altered bone remodeling. Pro-inflammatory cytokines such as TNF-α and IL-17 contribute to bone loss by modulating pathways including Wnt/β-catenin, which is inhibited by proteins like Dickkopf-1 (DKK-1) and sclerostin (SOST). Bone morphogenetic protein-6 (BMP-6) promotes osteoblast differentiation and bone formation. This study evaluated the association between serum levels of DKK-1, SOST, BMP-6, and bone mineral density (BMD) in AS patients treated with anti-TNF agents and conventional synthetic DMARDs (csDMARDs). Methods: A cross-sectional study included 76 AS patients diagnosed by modified New York criteria and 30 healthy donors matched by age and sex. BMD at the lumbar spine and hips was assessed by DXA in all participants. Disease activity (BASDAI) and functional index (BASFI) were measured in AS patients. Serum levels of DKK-1, SOST, BMP-6, TNF-α, and IL-17 were quantified by ELISA in both groups. AS patients were divided into two treatment groups: combined anti-TNFα and csDMARD therapy (n = 38), and only csDMARDs (n = 38). Results: Bone mineral density showed no significant statistical differences between the spine (p = 0.930) and hips (p = 0.876) in AS patients compared to healthy controls. The activity (BASDAI) and functionality (BASFI) scores were similar in both treatment groups (p = 0.161 and p = 0.271, respectively). No significant differences were found in serum levels of DKK-1 (p = 0.815), SOST (p = 0.771), BMP-6 (p = 0.451), or IL-17 (p = 0.335) between combined anti-TNFα and csDMARD therapy versus monotherapy with csDMARD. Conclusions: The combination of anti-TNF bDMARD therapy and csDMARD therapy is not significantly associated with serum levels of DKK-1, SOST, BMP-6, and BMD compared to those treated with csDMARD monotherapy in patients with AS. This study provides novel and clinically relevant evidence on how anti-TNF bDMARDs and csDMARDs differentially affect bone turnover biomarkers and bone health in patients with AS, contributing to a better understanding of therapeutic strategies and guiding future research and clinical decision-making. Full article

Recurrent facial palsy is a rare event in the pediatric population, mostly idiopathic or associated with common comorbidities or, rarely, observed in syndromic conditions. However, some cases are difficult to explain and need more accurate diagnostic approaches. In this work, we describe a pediatric case of recurrent facial palsy secondary to hyperostosis of the skull and narrowing of the neural foramina related to a SOST-related sclerosing bone dysplasia. To our knowledge, this is the first Italian case that is also related to a novel loss-of-function variant in the SOST gene. We highlight the clinical relevance of a proper early diagnosis and the need for correct monitoring of the clinical evolution, considering the natural history of the disease, to prevent/reduce severe neurological complications. Full article

Sociotechnical systems (STSs) are generally assumed to be systems that incorporate humans and technology, strongly depending on a sustainable equilibrium between the following nondeterministic social context ingredients: social structures, roles, and rights, as well as the designers’ Holy Grail, the deterministic nature of the underlying technical system. The fact that the relevant social concepts are more mature than the supporting technologies qualifies the digital transformation of sociotechnical systems as a reengineering rather than an engineering endeavor. Preserving the social mission throughout the digital transformation process in varying social contexts is mandatory, making the digital twins (DT) methodology application a contemporary research hotspot. In this research, we combined continuous transformation STS theory principles, an observer-based system-of-sociotechnical-systems (SoSTS) architecture model, and digital twinning methods to address common STS context representation challenges. Additionally, based on model-driven systems engineering methodology and meta-object-facility principles, the research specifies the universal meta-concepts and meta-modeling templates, supporting the creation of arbitrary sociotechnical systems’ external context digital twins. Due to the inherent diversity, significantly influenced by geopolitical, economic, and cultural influencers, a higher education external context specialization illustrates the reusability potentials of the proposed universal meta-concepts. Substituting higher-education-related meta-concepts and meta-models with arbitrary domain-dependent specializations further fosters the proposed universal meta-concepts’ reusability. Full article

Jabal Akhdar goats, native to Oman’s high-altitude Jabal Akhdar mountain range, are recognized for their high growth rate, remarkable twinning rate, and adaptability to harsh environmental conditions. This study assesses the genetic structure, inbreeding levels, effective population size (N_e), and linkage disequilibrium (LD) of Jabal Akhdar goats while identifying genomic regions under positive selection that may contribute to their environmental adaptation. The SNP genotypes from 72 Jabal Akhdar goats and two desert breeds from Egypt (153 Barki and 60 Saidi) revealed a clear genetic distinction between both groups. Within the Jabal Akhdar goats, genetic differentiation was also identified among the three sampled villages, indicating a village-specific genetic structure. The Jabal Akhdar breed exhibited a moderate level of inbreeding (F_ROH = 0.16), greater than that of the Barki and Saidi breeds. Additionally, Jabal Akhdar goats displayed greater LD and lower N_e levels compared to the Egyptian breeds. Analysis of runs of homozygosity (ROH) and extended haplotype homozygosity-based statistics (iHS and Rsb) identified 93 genomic regions exhibiting signatures of positive selection (80 from ROH, 5 from iHS, and 8 from Rsb). These regions harbor genes associated with traits essential for environmental adaptability, including hypoxia tolerance (SUCNR1, ANGPTL1, MITF, MTUS2), muscle development and function (MBNL1, ACTC1, CAPN5), fertility (GNRHR, CCNA1, SPAG1), UV radiation resistance (UVRAG, BRCA1), bone development (SOST, MEOX1), and lipid metabolism for energy utilization (DGAT2, G6PC, SUCLG2). The results of this study provide valuable insights for identifying causative variants and haplotypes underlying the Jabal Akhdar goat’s superior adaptability. These findings can guide breeders in designing conservation strategies and improving the productivity of this unique indigenous breed. Full article

Sclerostin (SOST) is a specific osteocyte protein. During the differentiation and proliferation of osteoblasts and osteoclasts, the high expression of SOST can inhibit bone formation and contribute to osteoporosis and the bone metastasis of malignant tumors. Most of the research on SOST has focused on bone cells, but studies have found that SOST is not a specific product of bone cells but that it is also expressed by articular chondrocytes. SOST can regulate the progression of osteoarthritis in bone and cartilage, promote subchondral bone sclerosis, and inhibit cartilage degeneration. A review of the literature found that SOST can not only regulate bone metabolism, but it is also expressed in cardiovascular, kidney, liver, and other tissues, influencing the occurrence and development of diseases in these organs and tissues. Studies have found that diseases of extra-bone organs, such as atherosclerosis, aneurysm, chronic kidney disease, and cirrhosis, may be related to the expression of SOST. Simultaneously, long-term exercise can reduce SOST levels, especially in areas of high bone strain. Prolonged exercise induces bone adaptation to mechanical stress, resulting in diminished responsiveness of bone cells to exercise and a reduction in serum SOST levels. Short-term acute exercise can elevate serum SOST levels, but these results are often limited by age, gender, and energy status. In general, serum SOST rises immediately after short-term acute exercise, returning to baseline or even decreasing after exercise. Full article

Sclerostin, encoded by the SOST gene, is a novel bone anabolic target for bone diseases. Humanized anti-sclerostin antibody, romosozumab, was approved for treatment of postmenopausal osteoporosis by the US Food and Drug Administration (FDA), but with a black-box warning on cardiovascular risk. The clinical data regarding cardiovascular events from various pre-marketing and post-marketing studies of romosozumab were inconsistent. Overall, the cardiovascular risk of sclerostin inhibition could not be excluded. The restriction of romosozumab in patients with cardiovascular disease history would be necessary. Moreover, genome-wide association study (GWAS) analyses of SOST variants revealed inconsistent results of the association between SOST variations and cardiovascular diseases. Further research incorporating larger sample sizes and functional analyses are necessary. In analyses of serum/tissue sclerostin levels in patients with cardiovascular diseases, the results were controversial but indicated an association between sclerostin and the presence/severity/outcomes of cardiovascular diseases. Nonclinical studies in rodents indicated the inhibitory effect of sclerostin on inflammation, aortic aneurysm, atherosclerosis, and vascular calcification. Sclerostin loop3 participated in the inhibitory effect of sclerostin on bone formation, while the cardiovascular protective effect of sclerostin was independent of sclerostin loop3. Macrophagic sclerostin loop2–apolipoprotein E receptor 2 (ApoER2) interaction participated in the inhibitory effect of sclerostin on inflammation in vitro. Sclerostin in human aortic smooth muscle cells participated in the reduction in calcium deposition. The role of sclerostin in cardiovascular system deserves further investigation. Full article

In this review paper, we will evaluate LRP4, a low-density lipoprotein receptor-related protein, and its many roles involving myasthenia gravis (MG), Wnt signaling, bone formation and craniofacial development. In MG, LRP4 is critical to the formation of the neuromuscular junction (NMJ) and the key function is to allow for controlled muscle contraction. LRP4 works in combination with agrin and MuSK to form the functional complex. In Wnt signaling, LRP4 was recently identified as a critical player in the pathway for both bone and tooth development and function. Its ability to act as an inhibitor sheds new light on bone formation and resorption. LRP4 binds sclerostin to LRP5 and LRP6, facilitating inhibitory effects important for bone homeostasis and remodeling. In this review paper, we will summarize the known roles of LRP4 as well as explore future directions for research surrounding LRP4 functionality. Full article

Background/Objectives: Osteoporosis and cardiovascular disease (CVD) share common risk factors and pathophysiological mechanisms, raising concerns about the cardiovascular implications of sclerostin inhibition. Romosozumab, a monoclonal antibody that targets sclerostin, is effective in increasing bone mineral density (BMD) and reducing fracture risk. However, evidence suggests that sclerostin inhibition may adversely affect vascular calcification, potentially increasing the risk of myocardial infarction (MI) and stroke. Methods: This review synthesizes data from clinical trials, such as ARCH, BRIDGE, and FRAME, alongside genetic studies and observational analyses, to evaluate the cardiovascular safety of romosozumab. PubMed was searched for relevant studies published within the last five years. Studies addressing the relationship between romosozumab and cardiovascular outcomes were included, emphasizing both its efficacy in osteoporosis management and potential cardiovascular risks. Results: Romosozumab significantly improves BMD and reduces fracture risk in postmenopausal women and men with osteoporosis. However, clinical trials report an increased incidence of major adverse cardiovascular events (MACE), particularly in patients with pre-existing cardiovascular conditions such as chronic kidney disease (CKD), diabetes, or prior CVD. Genetic studies indicate that SOST gene variants may also influence cardiovascular outcomes. Conclusions: While romosozumab is an effective treatment for osteoporosis, careful cardiovascular risk assessment is crucial before initiating therapy, especially for high-risk populations. Long-term studies are needed to evaluate chronic safety. Future therapeutic strategies should aim to maintain bone health while minimizing cardiovascular risks, ensuring a balance between efficacy and safety in osteoporosis treatment. Full article

This study explores how select microRNAs (miRNAs) influence bone structure in humans and in transgenic mice. In trabecular bone biopsies from 84 postmenopausal women (healthy, osteopenic, and osteoporotic), we demonstrate that DLEU2 (deleted in lymphocytic leukemia 2)-encoded miR-15a-5p is strongly positively associated with bone mineral density (BMD) at different skeletal sites. In bone transcriptome analyses, miR-15a-5p levels correlated positively with the osteocyte characteristic transcripts SOST (encoding sclerostin) and MEPE (Matrix Extracellular Phosphoglycoprotein), while the related miR-15b-5p showed a negative association with BMD and osteoblast markers. The data imply that these miRNAs have opposite roles in bone remodeling with distinct actions on bone cells. Expression quantitative trait loci (eQTL) variants confirmed earlier DLEU2 associations. Furthermore, a novel variant (rs12585295) showed high localization with transcriptionally active chromatin states in osteoblast primary cell cultures. The supposition that DLEU2-encoded miRNAs have an important regulatory role in bone remodeling was further confirmed in a transgenic mice model showing that miR-15a/16-1-deleted mice had significantly higher percentage bone volume and trabecular number than the wild type, possibly due to prenatal actions. However, the three-point mechanical break force test of mice femurs showed a positive correlation between strength and miR-15a-5p/miR-16-5p levels, indicating differential effects on cortical and trabecular bone. Moreover, these miRNAs appear to have distinct and complex actions in mice prenatally and in adult humans, impacting BMD and microstructure by regulating bone cell transcription. However, detailed interactions between these miRNAs and their downstream mechanisms in health and disease need further clarification. Full article