Search Results (195)

Biomorphic hydroxyapatite scaffolds derived from rattan wood (GreenBone) show significant promise in bone tissue engineering due to their inherent structural similarity to natural bone. Laser-drilled GreenBone scaffolds were studied for enhanced porosity, nutrient diffusion, cellular infiltration, and vascularisation. Patient-derived bone marrow mesenchymal stromal/stem cells (BMMSCs) and culture-expanded mesenchymal stem cells (cMSCs) demonstrated high cell viability (>90%), considerable adhesion, and extensive cytoskeletal organisation. Trilineage differentiation confirmed the multipotency of BMMSCs, with osteogenic, adipogenic, and chondrogenic markers being successfully expressed. BMMSCs and cMSCs exhibited enhanced differentiation and gene expression profiles. At week 4, key osteogenic and angiogenic genes such as BMP2, VEGFC, RUNX2, and COL1A1 showed elevated expression, indicating improved bone formation and vascularisation activity. Markers associated with extracellular matrix (ECM) remodelling, including MMP9 and TIMP1, were also upregulated, suggesting active tissue remodelling. ELISA analysis for VEGF further demonstrated increased VEGF secretion, highlighting the scaffold’s angiogenic potential. The improved cellular response and vascular signalling emphasise the translational relevance of laser-modified GreenBone scaffolds for bone tissue engineering, particularly for critical-sized defect repair requiring rapid vascularised bone regeneration. Full article

With the progress of global aging, osteoporosis, as a systemic bone disease, has become an increasingly serious public health problem. Osteoporosis has an insidious onset, and the fractures it causes have a high rate of disability and mortality. Early diagnosis and intervention of the disease are particularly important. Currently, diagnostic methods for osteoporosis, such as dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and bone turnover markers (BTM), all have their limitations. miRNA is a type of non-coding RNA that plays a role in the epigenetic regulation of gene expression. A large number of studies have shown that miRNA is involved in the formation and functional execution of osteoblasts. The differential expression of miRNA levels can effectively distinguish osteoporosis patients from normal individuals, and miRNA detection has the advantages of simple sample collection, non-invasive measurement, specificity for bone metabolism, correct correlation with standard techniques for bone remodeling analysis, and the ability to respond to the treatment of diseases affecting bone metabolism. This makes miRNAs potentially effective diagnostic markers for osteoporosis. This article aims to summarize our current understanding of miRNA regulation of osteoblast generation and function, and we will also discuss the potential value of these miRNAs as biomarkers for the diagnosis of osteoporosis. Full article

Mechanical stimulation critically regulates mesenchymal stem cell (MSC) differentiation, yet its effects in three-dimensional (3D) environments remain poorly defined. Here, we developed a custom dynamic stretcher integrating poly(dimethylsiloxane) (PDMS) chambers to apply cyclic strain to human MSCs encapsulated in Fmoc-diphenylalanine (Fmoc-FF) peptide hydrogels—a fully synthetic, tunable extracellular matrix mimic. Finite element modeling verified uniform strain transmission across the hydrogel. Dynamic stretching at 0.5 Hz and 10% strain induced pronounced cytoskeletal alignment, enhanced actin stress fiber formation (coherency index $\approx 0.85$), and significantly increased proliferation compared to static or high-frequency (2.5 Hz, 1%) conditions (coherency index $\approx 0.6$). Quantitative image analysis confirmed strain-dependent increases in coherency index and F-actin intensity, indicating enhanced mechanotransductive remodeling. Biochemical assays and qRT–PCR revealed 2–3-fold upregulation of osteogenic markers—RUNX2, ALP, COL1A1, OSX, BMP, ON, and IBSP—under optimal strain. These results demonstrate that low-frequency, high-strain mechanical loading in 3D peptide hydrogels activates RhoA/ROCK and YAP/TAZ pathways, driving osteogenic differentiation. The integrated experimental–computational approach provides a robust platform for studying mechanobiological regulation and advancing mechanically tunable biomaterials for bone tissue engineering. Full article

Background and Objectives: This study aims to analyze the effects of levetiracetam (LEV) and valproic acid (VPA) administration on oxidative stress, inflammation, apoptosis, extracellular matrix dynamics, and bone remodeling parameters in rat alveolar bone exposed to orthodontic force. Materials and Methods: Four experimental groups were designed for this study: Control, Force, Force + LEV, and Force + VPA. LEV (150 mg/kg/day) or VPA (300 mg/kg/day) was administered intraperitoneally to the experimental groups daily for 6 weeks. At the end of the experimental period, the alveolar bone tissues were used for molecular analyses. RT-PCR analysis was performed to assess the expression levels of antioxidant markers [superoxide dismutase, (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH)], inflammatory cytokines [tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)], apoptosis-related genes (Bax, Bcl-2, and Caspase-3), matrix remodeling genes [matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and metallopeptidase inhibitor 1 (TIMP-1)], and bone metabolism regulators [receptor activator of nuclear factor kappa-Β ligand (RANKL) and osteoprotegerin (OPG)]. Oxidative stress and inflammatory measurements were also confirmed via ELISA assays. Results: The results demonstrated that orthodontic force application increased oxidative stress, inflammation, and apoptosis compared to the Control group, disrupted extracellular matrix homeostasis, and increased bone resorption, while LEV administration (LEV + Force) markedly mitigated these abnormalities. In other words, LEV administration increased levels of antioxidant markers, decreased levels of inflammatory cytokines and pro-apoptotic genes, restored extracellular matrix balance (decrease in MMP-2 and MMP-9 with concurrent upregulation of TIMP-1), and limited tissue destruction (decrease in RANKL along with elevation in OPG). In contrast to LEV, VPA did not correct these molecular alterations induced by orthodontic force and, in several parameters, further exacerbated them. Conclusions: In conclusion, molecular data from the animal model indicate that LEV plays a protective role against orthodontic force by reducing excess levels of oxidative stress, apoptosis, and inflammation and homeostatic pathways. Full article

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., ACE, AGT, NOS3, VEGF, ADRA2A, ADRB1–3) were associated with endurance, cardiovascular regulation, and recovery. Genes related to muscle structure, metabolism, and hypertrophy (e.g., ACTN3, CKM, MLCK, TRIM63, TTN-AS1, HIF1A, MSTN, MCT1, AMPD1) were linked to sprint performance, metabolic efficiency, and muscle injury susceptibility. Neurotransmission-related genes (BDNF, COMT, DRD1–3, DBH, SLC6A4, HTR2A, APOE) influenced motivation, fatigue, cognitive performance, and brain injury recovery. Connective tissue and extracellular matrix genes (COL1A1, COL1A2, COL2A1, COL5A1, COL12A1, COL22A1, ELN, EMILIN1, TNC, MMP3, GEFT, LIF, HGF) were implicated in ligament, tendon, and muscle injury risk. Energy metabolism and mitochondrial function genes (PPARA, PPARG, PPARD, PPARGC1A, UCP1–3, FTO, TFAM) shaped endurance capacity, substrate utilization, and body composition. Oxidative stress and detoxification pathways (GSTM1, GSTP1, GSTT1, NRF2) influenced recovery and resilience, while bone-related variants (VDR, P2RX7, RANK/RANKL/OPG) were associated with bone density and remodeling. Beyond genomics, proteomics identified markers of muscle damage and repair, metabolomics characterized fatigue- and energy-related signatures, and microbiomics revealed links between gut microbial diversity, recovery, and physiological resilience. Evidence from omics research in soccer supports the potential for individualized approaches to training, nutrition, recovery, and injury prevention. By integrating genomics, proteomics, metabolomics, and microbiomics data, clubs and sports practitioners may design precision strategies tailored to each player’s biological profile. Future research should expand on multi-omics integration, explore gene–environment interactions, and improve representation across sexes, age groups, and competitive levels to advance precision sports medicine in soccer. Full article

Background. Glucocorticoid-induced osteoporosis represents a well-known type of secondary osteoporosis (SOp). While the most prevalent sub-category includes corticotherapy, another important contributor is represented by Cushing’s syndrome. In this traditional landscape, adrenal incidentalomas do not involve a standard cause of SOp, since most of them are non-functioning adrenal tumours (NFATs). Yet, 30–40% of them are not entirely “non-functioning”, due to mild autonomous cortisol secretion (MACS). Despite not being a guideline-based diagnosis, a lower ACTH might point to various NFATs/MACS complications. Objective. This study aimed to determine the relationship between the bone health status of post-menopausal women with NFATs/MACS and their baseline morning ACTH level. The bone health indicators were DXA, FRAX, and bone remodelling markers. Methods. This was a retrospective, real-life, transversal study in adult females who were hospitalized in a single tertiary centre of endocrinology. They were all anti-osteoporotic drug-naïve. The subjects underwent CT and DXA scanning and a 1 mg dexamethasone suppression test (DST). Results. The cohort (sample size of N = 84 patients, 61.49 ± 7.86 years) had a type 2 diabetes rate of 18%, arterial hypertension rate of 75%, and a dyslipidemia rate of 78%. Median ACTH was 11.89 pg/mL. The prevalence of MACS was 30.95%. The mean largest tumour diameter (LTD) was 2.25 ± 0.99 cm. ACTH correlated with second-day cortisol after the 1 mg DST (r = −0.301, p = 0.024), and LTD (r = −0.434, p < 0.001). ROC analysis for the bone resorption marker CrossLaps showed an AUC of 0.647 (p = 0.05), with the highest Youden index for the cut-off at 0.32 ng/mL (sensitivity 87.50%, specificity 39.50%). Bone impairment (osteoporosis + osteopenia) was found in 65% of patients, with an osteoporotic fracture prevalence of 4.76%. The lowest mean T-score (−1.12 ± 1.00) showed osteopenia, and the median trabecular bone score pointed a partially degraded microarchitecture [median (interquartile interval): 1.320 (1.230, 1.392)]. FRAX and FRAXplus estimations correlated with bone mineral density (BMD) at all three central DXA sites, regardless of the ACTH cut-off. Patients with a low ACTH (<10 pg/mL) displayed similar bone/adrenal features when compared to those with normal ACTH, except forbut they had a higher MACS rate (45.45% versus 21.57%, p = 0.021) and a larger LTD (2.67 ± 0.98 versus 1.98 ± 0.92 cm, p = 0.003). Fracture estimation showed that only in patients with a low ACTH, the 10-year fracture risk for major osteoporotic fractures (MOF) adjusted for lumbar BMD was lower than the risk for MOF adjusted for diabetes (p = 0.036), and the 10-year hip fracture risk was lower when adjusted for lumbar BMD (p = 0.007). ACTH correlated with lumbar BMD (r = 0.591, p = 0.002) only in the group with an ACTH < 10 pg/mL, suggesting its potential usefulness as a bone biomarker in these cases. On the other hand, MACS-negative subjects with a low ACTH versus those with a normal ACTH showed higher CrossLaps (0.60 ± 0.27 versus 0.42 ± 0.21 ng/mL, p = 0.022), indicating an elevated bone resorption even in patients with tumours that are regarded as true non-secretors. Conclusions. A subgroup of patients diagnosed with NFATs/MACS might be prone to skeletal damage, and biomarkers such as ACTH (specifically, suppressed ACTH) might serve as a surrogate pointer to help refine this higher risk in daily practice. Further research to address other ACTH cut-offs will place ACTH assays in the overall bone status evaluation in these patients, most probably not as a single biomarker, but in addition to other assays. Full article

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) promotes insulin secretion, lowers blood glucose levels, and is increasingly linked to bone remodeling. Native GIP is quickly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4), whereas (D-Ala²)GIP is a novel GIP analog engineered to resist DPP-4 degradation. Tumor necrosis factor-alpha (TNF-α), a key proinflammatory cytokine, promotes osteoclastogenesis and is notably upregulated during orthodontic tooth movement (OTM). This study aimed to evaluate the effects of (D-Ala²)GIP on TNF-α-induced osteoclast formation and bone resorption in vivo, as well as on OTM and related root resorption. Mice received daily supracalvarial injections of TNF-α with or without (D-Ala²)GIP for 5 days. The (D-Ala²)GIP-treated group showed significantly reduced osteoclast formation, bone resorption, and expression of osteoclastic markers TRAP and cathepsin K, compared to the group that received TNF-α alone. OTM was induced in mice by applying a nickel-titanium closed-coil spring, and mice were treated with either phosphate-buffered saline (PBS) or (D-Ala²)GIP every 2 days. After 12 days, the (D-Ala²)GIP-treated group showed significantly reduced tooth movement and fewer osteoclasts and odontoclasts on the compression side compared to the PBS control. These findings suggest that (D-Ala²)GIP inhibits OTM, potentially by suppressing TNF-α-driven osteoclastogenesis and bone resorption. Full article

This study aimed to investigate the effects of dietary manganese deficiency and compare the impact of manganese macroparticles (MnCO₃) and nanoparticles (Mn₂O₃NPs) on bone remodeling and metabolism. Twenty-seven male Wistar rats were divided into three groups (n = 9): control (standard MnCO₃, 65 mg Mn/kg), manganese-deficient, and Mn₂O₃NPs-supplemented (65 mg Mn/kg). After a 12-week feeding period, bone-related markers and gene expression were analyzed in the femur and blood. Mn-deficient rats showed reduced plasma levels of bone-specific alkaline phosphatase (BALP), tartrate-resistant acid phosphatase 5b (TRAP5b), interferon-β (IFN-β), RANKL glycoprotein, 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃), vitamin K₂, and collagen turnover markers (PINP, CTX-1, NTX). Femur levels of BALP, TRAP5b, interferon-γ (IFN-γ), osteonectin, calcitonin, PICP, PINP, and CTX-1 were also decreased. Replacing MnCO₃ with Mn₂O₃NPs increased IFN-γ but lowered IFN-β and 1,25-(OH)₂D₃ levels in plasma. This treatment also decreased the femur level of BALP and calcitonin, and the RANKL:OPG ratio, while increasing the expression level of Sp7 and Ctsk genes. To conclude, our results suggest that manganese deficiency is associated with suppressed bone turnover and altered mineral metabolism. Furthermore, replacing MnCO₃ with Mn₂O₃ nanoparticles did not yield the anticipated benefits for bone remodeling, as evidenced by the observed imbalances in osteogenic and resorptive markers, indicating a need for cautious evaluation of nanoparticle-based supplementation. Full article

Bone remodelling is a physiological process influenced by mechanical stimuli such as those generated during orthodontic treatment. Biochemical markers allow the phases of remodelling to be identified, its progression to be assessed, alterations to be detected and scaffold-based tissue regeneration to be evaluated. This study reviews the main markers involved in bone formation and resorption, highlighting their clinical relevance. A literature search was conducted in biomedical databases, selecting studies that analysed crevicular gingival fluid samples in areas of tension and compression. The markers were classified according to their function and location, and their baseline values, temporal variations and methods of analysis were compiled. Among the markers of bone formation, Osteoprotegerin (OPG), Transforming Growth factor β1 (TGF-β1) and Interleukin 27 (IL-27) stand out; while resorption markers include Receptor Activator of Nuclear Factor appa β Ligand (RANKL), Tumour Necrosis Factor (TNF-α) and Interleukin 1β (IL-1β). The results show different expression patterns depending on the type of force applied and the timing of the follow-up, allowing molecular profiles associated with each phase of remodelling to be established. This characterisation improves our understanding of tooth movement and provides a basis for the development of more precise scaffolds and functional biomaterials in orthodontics. Full article

Background and Objectives: Orthodontic tooth movement triggers micro-trauma in the periodontal ligament, leading to a balanced process of bone resorption and apposition mediated by local inflammatory responses. Monitoring N-telopeptide levels in gingival crevicular fluid (GCF) and applying low-intensity laser biostimulation can help optimize mechanical loading, reduce adverse effects, and enhance tissue remodeling during treatment. Materials and Methods: This study had a split-mouth observational design. From 30 patients with ages between 20 and 50, with standardized fixed orthodontic treatment, GCF samples were collected from both control and laser-treated hemiarches before and 14 days after appliance activation. Low-intensity laser therapy (LLLT) was applied to selected sites to assess its effect on N-telopeptide levels, a marker of bone resorption, with samples analyzed via ELISA and results compared statistically to evaluate the impact of laser biostimulation during orthodontic treatment. Statistical analysis was performed using paired t-tests or Wilcoxon tests for two-group comparisons. Results: N-telopeptide levels in gingival crevicular fluid increased significantly from baseline (T0) to 14 days (T1) in both the laser-treated (HL) and control (sham) hemiarches (HC), with higher values observed in the lasered side. Statistical analysis confirmed significant differences between HL and HC at T1 (p < 0.0001), as well as between each T1 group and baseline, indicating that low-intensity laser therapy enhanced bone resorption activity during orthodontic tooth movement. Conclusions: N-telopeptide exhibited higher values in the hemiarches where laser therapy was applied than in the control ones. This provides a rationale for using laser biostimulation as an adjuvant during orthodontic treatment to modulate tissue restructuring. Full article

Background/Objectives: Orthodontically induced bone remodeling is a complex process, driven by the interaction between osteoblasts, osteoclasts and various biochemical mediators, in response to mechanical forces applied to the teeth. Monitoring this process can be achieved by identifying biomarkers in gingival crevicular fluid (GCF), a dynamic and non-invasive method. Laser therapy, widely used in other medical fields for bio-stimulation and surgery, does not yet benefit from a standardized protocol in orthodontics. The aim of this study was to evaluate the advantages of using laser therapy during orthodontic treatment by analyzing osteocalcin (OC) in gingival crevicular fluid (GCF). Methods: Based on the inclusion and exclusion criteria, we selected 30 patients who presented dentoalveolar disharmony with crowding, who benefited from fixed orthodontic treatment, using edgewise brackets with the same slot size for all subjects. Laser therapy was performed randomly on one hemiarch (HL), right or left, for each patient, randomly chosen at time T0, after activation of the orthodontic appliance. On the other side, the control hemiarch (HC), the same protocol was followed, but without active light. Laser therapy was performed with a dental laser, with a power of 12 watts, setting the periodontology working mode. GCF was collected at baseline, before activation of the orthodontic appliance (time T0) and 14 days after its activation (time T1) from the control hemiarch (HC) and laser hemiarch (HL). Determination of OC levels, as a marker of bone apposition, was performed by the enzyme-linked immunosorbent assay (ELISA) method. To evaluate laser therapy, OC levels were assessed comparatively between HL and HC. Results: Comparing OC values at times T0 and T1 for HL, we obtained a statistically significant difference (p < 0.0001). No statistically significant difference was detected when comparing OC values in HC between T0 and T1 (p = 0.2422). A statistically significant difference was observed between HC and HL at T1 (p < 0.0001). Conclusions: The higher OC levels observed in the hemiarches where laser therapy was applied, compared to the controls, demonstrate its effectiveness as an adjuvant in bone remodeling during orthodontic treatment. Full article

For many years, menopause-related bone loss has been attributed solely to declining estrogen levels. Recently it has been suggested that bone loss accelerates during perimenopause, often preceding declines in estradiol (E₂), proposing that follicle-stimulating hormone (FSH), the levels of which are high during late perimenopause, may play a role in skeletal deterioration independently of E₂. The aim of this narrative review was to present aspects of bone health throughout the menopause transition with a focus on the relationship between FSH and bone-related outcomes. Epidemiological studies evaluating bone mineral density (BMD) and bone turnover markers (BTMs) were analyzed. Higher FSH levels were associated with reduced BMD, particularly at the spine and hip, as well as enhanced bone remodeling activity. In several longitudinal studies, FSH was found to be a more reliable predictor of bone loss than estrogen. In conclusion, FSH may serve as an early marker of perimenopausal bone health deterioration by identifying women at risk for bone loss and allowing for more personalized prevention strategies; however, further research is needed before its clinical use. Full article

Background: Crisponi/cold-induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder characterized by severe neonatal manifestations including paroxysmal muscle contractions, tendency for hyperthermia, and feeding and swallowing difficulties with high neonatal mortality. Pathogenic variants in the Cytokine Receptor-Like Factor 1 (CRLF1) gene have been associated with CS/CISS. These variants result in a loss of function of the encoded protein, which disrupts the formation of a functional heterodimer with Cardiotrophin-Like Cytokine Factor 1 (CLCF1). This complex is essential for the development of autonomic and sensory nervous systems, as well as for bone remodeling. We report two patients affected by CS harboring pathogenic variants in the CRLF1 gene. Methods—case reports: The first patient was diagnosed postnatally, presenting with non-epileptic paroxysmal events characterized by opisthotonus and orofacial contractions. He survived beyond infancy, later developing scoliosis and persistent episodes of hyperthermia. In the second patient, a prenatal ultrasound at 20 weeks of gestation revealed bilateral camptodactyly, also referred to as the ‘horn’s sign’, raising early suspicion of CS. The diagnosis was subsequently confirmed both clinically and genetically. After birth, the infant developed severe dysphagia, apnea, and paroxysmal events not associated with epileptiform activity on EEG. Sanger sequencing identified a homozygous c.708_709delinsT frameshift variant in the CRLF1 gene. The patient died at 30 days of age due to respiratory failure. Results and conclusions: With this manuscript, we aim to further delineate the phenotypic spectrum of this rare condition and propose the ‘horn’s sign’ as a targeted prenatal marker for early diagnosis in populations with known founder mutations or familial risk factors. Full article

Background: Oxidative stress and inflammation contribute to osteoporosis. Berries provide polyphenols especially anthocyanins that may modulate bone remodeling. This review is the first to synthesize evidence specifically on berries and bone health, integrating human, animal, and in vitro data under the GRADE framework. Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library through 23 April 2025 for human, animal, and in vitro studies on berries or berry-derived compounds and bone outcomes. Risk of bias was assessed with RoB 2.0, ROBINS-I, SYRCLE, and an adapted ToxRTool; certainty of human evidence was appraised with GRADE. Results: Nineteen studies were included (5 human, 9 in vivo, 5 in vitro). Observational cohorts linked higher anthocyanin intake with greater BMD. Small randomized trials suggested modest benefits of blackcurrant and blueberry on whole-body BMD, bone turnover markers, and calcium retention, while results for biomarkers were mixed. Animal models generally showed attenuation of ovariectomy- or age-related bone loss, and in vitro experiments indicated inhibition of osteoclastogenesis with stimulation of osteoblast activity. By GRADE, certainty was low–moderate for BMD, low for biomarkers, and very low for fractures. Conclusions: Berry polyphenols may support skeletal health via antioxidant and anti-resorptive mechanisms, but current clinical evidence is limited by small samples, heterogeneity, and lack of fracture outcomes. Larger, longer, standardized RCTs with exposure profiling are needed before dietary recommendations can be made. Full article

Our understanding of the different developmental origins of osteoclast progenitors and their respective roles during homeostatic bone remodeling at different skeletal sites as well as their roles within bone regeneration and degenerative conditions is evolving. In this narrative review article, we summarize what is known about the developmental origins, anatomical sources, and markers of osteoclast progenitors. We touch on how osteoclast progenitors vary during different disease contexts, including periodontitis, rheumatoid arthritis, and osteoarthritis. In addition, we also characterize osteoclast progenitors that contribute to bone healing and define changes observed with advancing age. In this regard, we offer a critical review of gaps within our understanding and opportunities for future development within the field. Because of their diverse nature under different contexts, identifying and characterizing osteoclast progenitors may help to advance condition-specific therapies. Full article