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Circulation Journal : Official Journal... May 2024The relationships of the clinical and biological attributes of epicardial adipose tissue (EAT) with aortic valve calcification (AVC) have not been characterized. We...
BACKGROUND
The relationships of the clinical and biological attributes of epicardial adipose tissue (EAT) with aortic valve calcification (AVC) have not been characterized. We evaluated the relationships of the clinical and histological features of EAT with AVC assessed using computed tomography (CT).Methods and Results: We enrolled 43 patients undergoing cardiac CT examination prior to elective cardiac surgery in whom AVC was identified on CT. EAT volume and density, coronary calcium score (CCS), AVC score (AVCS), and coronary atherosclerosis on CT angiography were evaluated in each patient. During cardiac surgery, 2 EAT samples were obtained for immunohistochemistry. The number of CD68- and CD11c-positive macrophages and osteocalcin-positive cells was counted in 6 random high-power fields of EAT sections. EAT density, but not EAT volume normalized to body surface area, was positively correlated with the number of macrophages and osteocalcin-positive cells in EAT. There was a positive correlation between ln(AVCS), but not ln(CCS+1), and the number of macrophages and osteocalcin-positive cells in EAT. Multivariate analysis revealed significant positive correlations for ln(AVCS) with EAT density (β=0.42; P=0.0072) and the number of CD68-positive macrophages (β=0.57; P=0.0022), CD11c-positive macrophages (β=0.62; P=0.0003), and osteocalcin-positive cells (β=0.52; P=0.0021) in EAT.
CONCLUSIONS
Inflammation and osteogenesis in EAT, reflected by high CT density, are associated with the severity of AVC representing aortic valve degeneration.
PubMed: 38763753
DOI: 10.1253/circj.CJ-24-0226 -
Frontiers in Cell and Developmental... 2024Prohibitin (PHB) is an essential scaffold protein that modulates signaling pathways controlling cell survival, metabolism, inflammation, and bone formation. However,...
Prohibitin (PHB) is an essential scaffold protein that modulates signaling pathways controlling cell survival, metabolism, inflammation, and bone formation. However, its specific role in periodontium development remains less understood. This study aims to elucidate the expression pattern and function of PHB in periodontium development and its involvement in alveolar bone formation. Immunolocalization of PHB in the periodontium of postnatal (PN) mice were examined. morpholino was micro-injected into the right-side mandible at PN5, corresponding to the position where the alveolar bone process forms in relation to the lower first molar. The micro-injection with a scramble control (PF-127) and the left-side mandibles were used as control groups. Five days post-micro-injection, immunohistochemical analysis and micro-CT evaluation were conducted to assess bone mass and morphological changes. Additionally, expression patterns of signaling molecules were examined following downregulation using 24-h cultivation of developing dental mesenchyme at E14.5. The immunostaining of PHB showed its localization in the periodontium at PN5, PN8, and PN10. The cultivation of dental mesenchyme resulted in alterations in Bmps, Runx2, and Wnt signalings after knock-down. At 5 days post-micro-injection, knocking down showed weak immunolocalizations of runt-related transcription factor (RUNX2) and osteocalcin (OCN). However, knocking down led to histological alterations characterized by decreased bone mass and stronger localizations of Ki67 and PERIOSTIN in the periodontium compared 1 to control groups. The micro-CT evaluation showed decreased bone volume and increased PDL space in the knock-down specimens, suggesting its regulatory role in bone formation. The region-specific localization of PHB in the margin where alveolar bone forms suggests its involvement in alveolar bone formation and the differentiation of the periodontal ligament. Overall, our findings suggest that plays a modulatory role in alveolar bone formation by harmoniously regulating bone-forming-related signaling molecules during periodontium development.
PubMed: 38756696
DOI: 10.3389/fcell.2024.1369634 -
Journal of Applied Oral Science :... 2024Studies have highlighted numerous benefits of ozone therapy in the field of medicine and dentistry, including its antimicrobial efficacy against various pathogenic...
OBJECTIVE
Studies have highlighted numerous benefits of ozone therapy in the field of medicine and dentistry, including its antimicrobial efficacy against various pathogenic microorganisms, its ability to modulate the immune system effectively, reduce inflammation, prevent hypoxia, and support tissue regeneration. However, its effects on dental extraction healing remain to be elucidated. .Therefore, this study aimed to evaluate the effects of systemically administered ozone (O3) at different doses in the healing of dental extraction sockets in rats.
METHODOLOGY
To this end, 72 Wistar rats were randomly divided into four groups after extraction of the right upper central incisor: Group C - control, no systemic treatment; Group OZ0.3 - animals received a single dose of 0.3 mg/kg O3; Group OZ0.7 - a single dose of 0.7 mg/kg O3; and Group OZ1.0 - a single dose of 1.0 mg/kg O3, intraperitoneally. In total, six animals from each group were euthanized at 7, 14, and 21 days after the commencement of treatment. Bone samples were harvested and further analyzed by descriptive histology, histomorphometry, and immunohistochemistry for osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) protein expression.
RESULTS
All applied doses of O3 were shown to increase the percentage of bone tissue (PBT) after 21 days compared to group C. After 14 days, the OZ0.7 and OZ1.0 groups showed significantly higher PBT when compared to group C. The OZ1.0 group presented the most beneficial results regarding PBT among groups, which denotes a dose-dependent response. OCN immunostaining was higher in all groups at 21 days. However, after seven and 14 days, the OZ1.0 group showed a significant increase in OCN immunostaining compared to C group. No differences in TRAP+ osteoclasts were found between groups and time points.
CONCLUSION
Therefore, O3 therapy at higher doses might be beneficial for bone repair of the alveolar socket following tooth extraction.
Topics: Animals; Ozone; Rats, Wistar; Tooth Extraction; Tooth Socket; Wound Healing; Tartrate-Resistant Acid Phosphatase; Immunohistochemistry; Osteocalcin; Time Factors; Male; Random Allocation; Reproducibility of Results; Treatment Outcome; Reference Values
PubMed: 38747807
DOI: 10.1590/1678-7757-2023-0412 -
Frontiers in Endocrinology 2024To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in...
PURPOSE
To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively.
METHODS
We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT and FT before and after treatment (FT-P/FT-A, FT-P/FT-A) on whether BTMs recovered.
RESULTS
The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT-P/FT-A and FT-P/FT-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05).
CONCLUSION
BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT decreased more than 51% and FT dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.
Topics: Humans; Male; Female; Graves Disease; Adult; Biomarkers; Retrospective Studies; Middle Aged; Bone Remodeling; Predictive Value of Tests; Thyroid Gland; Bone and Bones; Thyroid Hormones; Case-Control Studies; Prognosis; Antithyroid Agents; Thyroxine; Triiodothyronine; Follow-Up Studies
PubMed: 38742199
DOI: 10.3389/fendo.2024.1301213 -
Bone Reports Jun 2024Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone...
Dairy consumption, bone turnover biomarkers, and osteo sono assessment index in Japanese adults: A cross-sectional analysis of data from the Iwaki Health Promotion Project.
PURPOSE
Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone biomarkers in the Japanese population remain unclear. This study explored the association between dairy consumption and bone biomarkers in Japanese adults.
METHODS
This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. In total, 1063 adults were included in the analysis. Bone turnover marker levels were measured in local citizens during their annual medical checkups. The calcaneus osteo sono assessment index (OSI) was calculated using a quantitative ultrasound technique. The dietary intake of foods and nutrients was estimated using a food frequency questionnaire. Linear regression models were established using dairy consumption and bone biomarkers with adjustments. Statistic significance was considered by < 0.05.
RESULTS
In multivariate models, the tartrate-resistant acid phosphatase 5b and parathyroid hormone concentrations were inversely associated with dietary dairy consumption after adjusting for age and sex. The undercarboxylated osteocalcin, a procollagen type I N-terminal peptide to bone alkaline phosphatase ratio, and OSI were the directly associated with dairy consumption in multivariate models with adjustment.
CONCLUSIONS
Dairy consumption is partially associated with bone turnover biomarkers and OSI in adult Japanese participants. Habitual consumption of dairy foods may contribute to the nutritional supplementation for maintaining bone health, including turnover and structure.
CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE WHERE IT WAS OBTAINED
The Japanese Clinical Trials Registry (UMIN000040459), https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000046175.
PubMed: 38736771
DOI: 10.1016/j.bonr.2024.101770 -
Journal of Periodontal & Implant Science Apr 2024The aim of this study was to evaluate the effects of Frondoside A (FA) on the osteogenic differentiation of human periodontal ligament (PDL) cells.
PURPOSE
The aim of this study was to evaluate the effects of Frondoside A (FA) on the osteogenic differentiation of human periodontal ligament (PDL) cells.
METHODS
Human PDL cells were cultured in osteogenic medium and treated with FA at concentrations of 0, 0.05, and 0.2 µM for 14 days. The expression levels of genes associated with osteogenic differentiation were assessed using quantitative real-time polymerase chain reaction analysis. Subsequently, RNA sequencing was performed to identify enriched gene sets following FA treatment. Alkaline phosphatase (ALP) activity was measured to confirm the osteogenic potential of FA.
RESULTS
Treatment with 0.2 µM FA significantly increased the expression levels of runt-related transcription factor 2 (), , and osteocalcin () at day 3, while also significantly elevating the expression of dentin sialophosphoprotein (), , , , and osterix () at day 14 (<0.017). Hallmark gene sets enriched during FA treatment were associated with the KRAS (normalized enrichment score [NES]=2.02, =0.000), interferon alpha (IFN-α) (NES=1.88, =0.001), IFN-γ (NES=1.85, <0.001), hypoxia (NES=1.79, =0.001), and p53 (NES=1.77, =0.001) signaling pathways. Additionally, treatment with 0.2 µM FA significantly intensified ALP staining at day 14 (<0.05).
CONCLUSIONS
Within the limitations of this study, FA treatment influenced periodontal regeneration by promoting the osteogenic differentiation of human PDL cells.
PubMed: 38725429
DOI: 10.5051/jpis.2303840192 -
Orthopaedic Surgery Jun 2024The micro-nano structure of 3D-printed porous titanium (Ti) alloy with excellent performance in avoiding stress shielding and promoting bone tissue differentiation...
OBJECTIVES
The micro-nano structure of 3D-printed porous titanium (Ti) alloy with excellent performance in avoiding stress shielding and promoting bone tissue differentiation provides a new opportunity for the development of bone implants, but it necessitates higher requirements for bone tissue differentiation and the antibacterial properties of bone implants in clinical practice.
METHODS
This study investigated the preparation, antimicrobial properties, and osteogenesis-promoting ability of the 3D printed porous Ti alloy anodic oxidized Ag-carrying (Ag@3D-TiO) scaffolds. The 3D printed porous Ti alloy (3D-Ti), anodized 3D printed porous Ti alloy (3D-TiO), and Ag@3D-TiO scaffolds were synthesized using electron beam melting. The antimicrobial properties of the scaffolds were examined using antibacterial tests and their cytocompatibility was assessed using a cell proliferation assay and acridine orange/ethidium bromide (AO/EB) staining. In vitro cellular assays were used to investigate the effects of the scaffold microstructural features on cell activity, proliferation, and osteogenesis-related genes and proteins. In vivo animal experiments were used to evaluate the anti-inflammatory and osteogenesis-promoting abilities of the scaffolds.
RESULTS
The Ag@3D-TiO scaffolds exhibited sustained anti-microbial activity over time, enhanced cell proliferation, facilitated osteogenic differentiation, and increased extracellular matrix mineralization. In addition, alkaline phosphatase (ALP), collagen type I (COL-I), and osteocalcin (OCN)-related genes and proteins were upregulated. In vivo animal implantation experiments, the anti-inflammatory effect of the Ag@3D-TiO scaffolds were observed using histology, and a large amount of fibrous connective tissue was present around it; the Ag@3D-TiO scaffolds were more bio-compatible with the surrounding tissues compared with 3D-Ti and 3D-TiO; a large amount of uniformly distributed neoplastic bone tissue existed in their pores, and the chronic systemic toxicity test showed that the 3D-Ti, 3D-TiO, and Ag@3D-TiO scaffolds are biologically safe.
CONCLUSION
The goal of this study was to create a scaffold that exhibits antimicrobial properties and can aid bone growth, making it highly suitable for use in bone tissue engineering.
Topics: Titanium; Osteogenesis; Tissue Scaffolds; Silver; Animals; Printing, Three-Dimensional; Mice; Cell Proliferation; Cell Differentiation; Anti-Bacterial Agents; Porosity
PubMed: 38706035
DOI: 10.1111/os.14081 -
Journal For Immunotherapy of Cancer May 2024Skeletal morbidity in patients with cancer has a major impact on the quality of life, and preserving bone health while improving outcomes is an important goal of modern...
BACKGROUND
Skeletal morbidity in patients with cancer has a major impact on the quality of life, and preserving bone health while improving outcomes is an important goal of modern antitumor treatment strategies. Despite their widespread use in early disease stages, the effects of immune checkpoint inhibitors (ICIs) on the skeleton are still poorly defined. Here, we initiated a comprehensive investigation of the impact of ICIs on bone health by longitudinal assessment of bone turnover markers in patients with cancer and by validation in a novel bioengineered 3D model of bone remodeling.
METHODS
An exploratory longitudinal study was conducted to assess erum markers of bone resorption (C-terminal telopeptide, CTX) and formation (procollagen type I N-terminal propeptide, PINP, and osteocalcin, OCN) before each ICI application (programmed cell death 1 (PD1) inhibitor or programmed death-ligand 1 (PD-L1) inhibitor) for 6 months or until disease progression in patients with advanced cancer and no evidence of bone metastases. To validate the in vivo results, we evaluated osteoclast (OC) and osteoblast (OB) differentiation on treatment with ICIs. In addition, their effect on bone remodeling was assessed by immunohistochemistry, confocal microscopy, and proteomics analysis in a dynamic 3D bone model.
RESULTS
During the first month of treatment, CTX levels decreased sharply but transiently. In contrast, we observed a delayed increase of serum levels of PINP and OCN after 4 months of therapy. In vitro, ICIs impaired the maturation of preosteoclasts by inhibiting STAT3/NFATc1 signaling but not JNK, ERK, and AKT while lacking any direct effect on osteogenesis. However, using our bioengineered 3D bone model, which enables the simultaneous differentiation of OB and OC precursor cells, we confirmed the uncoupling of the OC/OB activity on exposure to ICIs by demonstrating impaired OC maturation along with increased OB differentiation.
CONCLUSION
Our study indicates that the inhibition of the PD1/PD-L1 signaling axis interferes with bone turnover and may exert a protective effect on bone by indirectly promoting osteogenesis.
Topics: Humans; Bone Remodeling; Male; Female; Prospective Studies; Immune Checkpoint Inhibitors; Middle Aged; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Aged; Longitudinal Studies; Neoplasms; Adult
PubMed: 38702145
DOI: 10.1136/jitc-2023-008669 -
International Dental Journal Apr 2024The present study aimed to (1) investigate biocompatibility and cytotoxicity of pulp-capping materials on viability of human dental pulp stem cells (hDPSCs); (2)...
OBJECTIVES
The present study aimed to (1) investigate biocompatibility and cytotoxicity of pulp-capping materials on viability of human dental pulp stem cells (hDPSCs); (2) determine angiogenic, odontogenic, and osteogenic marker mRNA expressions; and (3) observe changes in surface morphology of the hDPSCs using scanning electron microscopy (SEM).
METHODS
Impacted third molars were used to isolate the hDPSCs, which were treated with extract-release fluids of the pulp-capping materials (Harvard BioCal-Cap, NeoPUTTY MTA, TheraCal LC, and Dycal). Effects of the capping materials on cell viability were assessed using 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay and the apoptotic/necrotic cell ratios and reactive oxygen species (ROS) levels from flow cytometry. Marker expressions (alkaline phosphatase [ALP], osteocalcin [OCN], collagen type I alpha 1 [Col1A], secreted protein acidic and rich in cysteine [SPARC], osteonectin [ON], and vascular endothelial growth factor [VEGF]) were determined by quantitative reverse-transcription polymerase chain reaction. Changes in surface morphology of the hDPSCs were visualised by SEM.
RESULTS
The MTS assay results at days 1, 3, 5, and 7 indicated that Harvard BioCal-Cap, NeoPUTTY MTA, and TheraCal LC did not adversely affect cell viability when compared with the control group. According to the MTS assay results at day 14, no significant difference was found amongst Dycal, Harvard BioCal-Cap, NeoPUTTY MTA, and TheraCal LC affecting cell viability. Dycal was the only capping material that increased ROS level. High levels of VEGF expression were observed with Harvard BioCal-Cap, TheraCal LC, and NeoPUTTY MTA. NeoPUTTY MTA, and Dycal upregulated OCN expression, whereas TheraCal LC upregulated Col1A and SPARC expression. Only Dycal increased ALP expression. HDSCs were visualized in characteristic spindle morphology on SEM when treated with TheraCal LC and Harvard BioCal-Cap.
CONCLUSIONS
NeoPUTTY MTA and Harvard BioCal-Cap showed suitable biocompatibility values; in particular, these pulp-capping materials were observed to support the angiogenic marker.
PubMed: 38692961
DOI: 10.1016/j.identj.2024.04.006 -
World Journal of Diabetes Apr 2024Icariin (ICA), a natural flavonoid compound monomer, has multiple pharmacological activities. However, its effect on bone defect in the context of type 1 diabetes...
BACKGROUND
Icariin (ICA), a natural flavonoid compound monomer, has multiple pharmacological activities. However, its effect on bone defect in the context of type 1 diabetes mellitus (T1DM) has not yet been examined.
AIM
To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.
METHODS
The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining, alizarin red S staining, quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis. A bone defect model was established in T1DM rats. The model rats were then treated with ICA or placebo and micron-scale computed tomography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.
RESULTS
ICA promoted bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation. The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers (alkaline phosphatase and osteocalcin) and angiogenesis-related markers (vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1) compared to the untreated group. ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs. In the bone defect model T1DM rats, ICA facilitated bone formation and CD31EMCN type H-positive capillary formation. Lastly, ICA effectively accelerated the rate of bone formation in the defect area.
CONCLUSION
ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.
PubMed: 38680705
DOI: 10.4239/wjd.v15.i4.769