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Biology Nov 2023(1) Background: Biphasic bioceramics are synthetic bone substitutes that provide greater safety and better predictability in guided bone regeneration. This study aimed...
(1) Background: Biphasic bioceramics are synthetic bone substitutes that provide greater safety and better predictability in guided bone regeneration. This study aimed to evaluate the bone repair process using a new biphasic bioceramic of synthetic origin (Plenum Oss-70HA: 30β-TCP) in critical calvarial defects. (2) Methods: seventy-four defects were created in rat calvaria and divided into two groups-Plenum Oss (PO), right side, and Straumann BoneCeramic™ (BC), left side. Euthanasia was performed at 7, 15, 30, and 60 days after surgery. (3) Results: Lower gene expression was observed for runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor (VEGF) and higher expression for Integrin Binding Sialoprotein (IBSP). The results correlated with moderate immunolabeling for osteocalcin (OCN) and slight immunolabeling for osteopontin (OPN) in the PO group. Histometry showed a greater amount of biomaterial remaining in the PO group at 60 days. The microtomographic analysis showed a lower density of bone connectivity and a greater thickness of the trabeculae for the remnants of the PO group. (4) Conclusions: the Plenum Oss showed no differences compared to BoneCeramic™ and is therefore considered an effective option as a synthetic bone substitute in bone regeneration.
PubMed: 37998016
DOI: 10.3390/biology12111417 -
Brazilian Oral Research 2023This study aimed to investigate whether GSK-3 inhibition (CHIR99021) effectively promoted mineralization by cementoblasts (OCCM-30). OCCM-30 cells were used and treated...
This study aimed to investigate whether GSK-3 inhibition (CHIR99021) effectively promoted mineralization by cementoblasts (OCCM-30). OCCM-30 cells were used and treated with different concentrations of CHIR99021 (2.5, 5, and 10 mM). Experiments included proliferation and viability, cellular metabolic activity, gene expression, and mineral nodule formation by Xylene Orange at the experimental time points. In general, CHIR99021 did not significantly affect OCCM-30 viability and cell metabolism (MTT assay) (p > 0.05), but increased OCCM-30 proliferation at 2.5 mM on days 2 and 4 (p < 0.05). Data analysis further showed that inhibition of GSK-3 resulted in increased transcript levels of Axin2 in OCCM-30 cells starting as early as 4 h, and regulated the expression of key bone markers including alkaline phosphatase (Alp), runt-related transcription factor 2 (Runx-2), osteocalcin (Ocn), and osterix (Osx). In addition, CHIR99021 led to an enhanced mineral nodule formation in vitro under both osteogenic and non-osteogenic conditions as early as 5 days after treatment. Altogether, the results of the current study suggest that inhibition of GSK-3 has the potential to promote cementoblast differentiation leading to increased mineral deposition in vitro.
Topics: Dental Cementum; Glycogen Synthase Kinase 3; Cell Proliferation; Osteocalcin; Cell Differentiation
PubMed: 37970932
DOI: 10.1590/1807-3107bor-2023.vol37.0112 -
European Journal of Medical Research Nov 2023Kaempferol has demonstrated notable positive effects on the osteogenic differentiation of mesenchymal stem cells (MSC) and osteoblasts. A substantial body of research...
Kaempferol has demonstrated notable positive effects on the osteogenic differentiation of mesenchymal stem cells (MSC) and osteoblasts. A substantial body of research has emphasized the role of dislodged titanium particles in aseptic loosening following joint replacement surgery. This study predominantly investigates the suppressive influence of Kaempferol on osteolysis induced by titanium (Ti) alloy particles. In vitro investigations disclosed that Kaempferol effectively enhanced mineralization and alkaline phosphatase (ALP) activity in bone-marrow mesenchymal stem cells exposed to Ti particles. In addition, we conducted a comprehensive analysis of osteogenic differentiation microarray data_sets (GSE37676, GSE79814, and GSE114474) to identify differentially expressed genes. Significantly, Kaempferol upregulated the expression of critical osteogenic markers, including Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), osterix/Sp-7, and β-catenin. In vivo experiments, including H&E staining and Immunohistochemistry, provided compelling evidence that Kaempferol exerted a robust inhibitory effect on periprosthetic osteolysis in mice, with particularly pronounced results at higher doses. Moreover, it elevated the expression levels of osteogenic factors and Wnt/β-catenin signaling components. These findings collectively indicate that Kaempferol mitigates the hindrance to osteogenesis posed by titanium particles by activating the Runx2 and Wnt/β-catenin signaling pathways. This research lays a solid foundation for the prospective utilization of Kaempferol in the management of aseptic loosening following arthroplasty, offering promising therapeutic potential.
Topics: Animals; Mice; beta Catenin; Cell Differentiation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Kaempferols; Osteogenesis; Osteolysis; Prospective Studies; Titanium; Wnt Signaling Pathway
PubMed: 37946300
DOI: 10.1186/s40001-023-01469-w -
Nutricion Hospitalaria Jun 2024Introduction: the prevalence of osteoporosis among candidates for lung transplantation is high and its pathophysiology is multifactorial. Objectives: to evaluate...
Introduction: the prevalence of osteoporosis among candidates for lung transplantation is high and its pathophysiology is multifactorial. Objectives: to evaluate differences in bone mineral density, risk of fractures and bone remodeling markers in patients with terminal lung disease, at the time they are evaluated for lung transplantation, comparing two types of pathologies. Material and methods: fifty-nine subjects, proposed to receive a lung transplant due to advanced lung disease, were included in this study. They were divided into two groups according to their respiratory pathology: chronic obstructive pulmonary disease (COPD) and diffuse interstitial pulmonary disease (ILD). Demographic data were collected and bone densitometry, blood analysis with markers of bone remodeling, spirometry, six-minute walk test (6MWT), echocardiography and cardiac catheterization were performed Results: no differences were found between the groups, regarding their age, sex, BMI or exposure to tobacco. A higher prevalence of osteoporosis and a higher FRAX were observed in the group with COPD. Regarding bone remodeling markers, higher parathyroid hormone (PTH) and higher osteocalcin were found in the COPD group. Vitamin D was lower in COPD patients. Conclusions: two out of three of the patients evaluated for lung transplantation had osteopenia or osteoporosis. The prevalence of osteoporosis and FRAX is higher in COPD patients. Vitamin D supplementation should be considered in certain patients. Differences in bone remodeling markers may be useful for suspected osteoporosis and therapeutic management.
Topics: Humans; Lung Transplantation; Male; Female; Middle Aged; Osteoporosis; Pulmonary Disease, Chronic Obstructive; Bone Density; Aged; Bone Remodeling; Lung Diseases, Interstitial; Bone and Bones; Adult; Biomarkers; Prevalence
PubMed: 37929858
DOI: 10.20960/nh.04845 -
Journal of Cellular and Molecular... Jan 2024The effect of preosteoblast-derived exosomes on bone marrow macrophages (BMMΦ) and calvarial osteoblasts (cOB) was evaluated in vitro, and bone formation studies were...
The effect of preosteoblast-derived exosomes on bone marrow macrophages (BMMΦ) and calvarial osteoblasts (cOB) was evaluated in vitro, and bone formation studies were performed in vivo in mice. Preosteoblastic MC3T3-E1 clone 4 (MC4) cell-derived exosomes (MC4exo) were characterized with particle tracking, transmission electron microscopy and western blot analysis to validate size, number, shape and phenotypic exosome markers. Exosomes pre-labelled with PKH67 were incubated with BMMΦ and phagocytosis of exosomes was confirmed. To examine the effect of MC4exo on macrophage polarization, BMMΦ were treated with MC4exo and the expression of pro- and anti-inflammatory cytokines was determined by qPCR. MC4exo treatment upregulated mRNA expression of Cd86, Il1β, Ccl2, Rankl and Nos, and downregulated Cd206, Il10 and Tnfα, suggesting a shift towards pro-inflammatory 'M1-like' macrophage polarization. Combination of RANKL and MC4exo increased osteoclast differentiation of BMMΦ in comparison to RANKL alone as analysed by TRAP staining. MC4exo treatment showed no significant effect on calvarial osteoblast mineralization. For in vivo studies, intratibial inoculation of MC4exo (2 × 10 particles in PBS, n = 12) and vehicle control (PBS only, n = 12) was performed in C57Bl/6 mice (8 weeks, male). Micro-CT analyses of the trabecular and cortical bone compartments were assessed at 4 weeks post-injection. Tibial sections were stained for TRAP activity to determine osteoclast presence and immunofluorescence staining was performed to detect osteocalcin (Ocn), osterix (Osx) and F4/80 expression. Intratibial inoculation of MC4exo increased the diaphyseal bone mineral density and trabecular bone volume fraction due to increased trabecular number. This increase in bone was accompanied by a reduction in bone marrow macrophages and osteoclasts at the experimental endpoint. Together, these findings suggest that preosteoblast-derived exosomes enhanced bone formation by influencing macrophage responses.
Topics: Male; Animals; Mice; Exosomes; Bone and Bones; Osteoclasts; Macrophages; Osteoblasts; Cell Differentiation
PubMed: 37929757
DOI: 10.1111/jcmm.18029 -
PloS One 2023In this study, we have firstly elucidated that serum starvation augmented the levels of human GD3 synthase (hST8Sia I) gene and ganglioside GD3 expression as well as...
In this study, we have firstly elucidated that serum starvation augmented the levels of human GD3 synthase (hST8Sia I) gene and ganglioside GD3 expression as well as bone morphogenic protein-2 and osteocalcin expression during MG-63 cell differentiation using RT-PCR, qPCR, Western blot and immunofluorescence microscopy. To evaluate upregulation of hST8Sia I gene during MG-63 cell differentiation by serum starvation, promoter area of the hST8Sia I gene was functionally analyzed. Promoter analysis using luciferase reporter assay system harboring various constructs of the hST8Sia I gene proved that the cis-acting region at -1146/-646, which includes binding sites of the known transcription factors AP-1, CREB, c-Ets-1 and NF-κB, displays the highest level of promoter activity in response to serum starvation in MG-63 cells. The -731/-722 region, which contains the NF-κB binding site, was proved to be essential for expression of the hST8Sia I gene by serum starvation in MG-63 cells by site-directed mutagenesis, NF-κB inhibition, and chromatin immunoprecipitation (ChIP) assay. Knockdown of hST8Sia I using shRNA suggested that expressions of hST8Sia I and GD3 have no apparent effect on differentiation of MG-63 cells. Moreover, the transcriptional activation of hST8Sia I gene by serum starvation was strongly hindered by SB203580, a p38MAPK inhibitor in MG-63 cells. From these results, it has been suggested that transcription activity of hST8Sia I gene by serum starvation in human osteosarcoma MG-63 cells is regulated by p38MAPK/NF-κB signaling pathway.
Topics: Humans; Transcriptional Activation; Up-Regulation; NF-kappa B; Gene Expression Regulation, Enzymologic; Cell Differentiation; Gene Expression
PubMed: 37917776
DOI: 10.1371/journal.pone.0293321 -
Heliyon Oct 2023Basic medical studies have reported an improved effect of osteocalcin on cognition. We explored the causal link between osteocalcin and dementia via the implementation...
OBJECTIVE
Basic medical studies have reported an improved effect of osteocalcin on cognition. We explored the causal link between osteocalcin and dementia via the implementation of Mendelian randomization methodology.
METHODS
Genome-wide association studies were employed to identify single nucleotide polymorphisms (SNPs) showing significant correlations with osteocalcin. Subsequently, A two-sample Mendelian randomization analysis was conducted utilizing the inverse-variance-weighted (IVW) technique to assess the causal relationship between osteocalcin and various types of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), and vascular dementia (VD). This approach aimed to minimize potential sources of confounding bias and provide more robust results. Multivariable MR (MVMR) analysis was conducted to adjust for potential genetic pleiotropy.
RESULTS
The study employed three SNPs, namely rs71631868, rs9271374, and rs116843408, as genetic tools to evaluate the causal association of osteocalcin with dementia. The IVW analysis indicated that osteocalcin may have a potential protective effect against AD with an odds ratio (OR) of 0.790 (95 % CI: 0.688-0.906; P < 0.001). However, no significant relationship was observed between osteocalcin and other types of dementia. Furthermore, the MVMR analysis indicated that the impact of osteocalcin on AD remained consistent even after adjusting for age-related macular degeneration and Type 2 diabetes with an OR of 0.856 (95 % CI: 0.744-0.985; P = 0.030).
CONCLUSIONS
Our findings provide important insights into the role of osteocalcin in the pathogenesis of AD. Future research is required to clarify the underlying mechanisms and their clinical applications.
PubMed: 37916108
DOI: 10.1016/j.heliyon.2023.e21073 -
Journal of Orthopaedic Surgery and... Nov 2023Antiepileptic drugs (AEDs) harm bone health and are significantly associated with osteoporosis development. In this study, we aimed to explore the mechanisms involved in...
BACKGROUND
Antiepileptic drugs (AEDs) harm bone health and are significantly associated with osteoporosis development. In this study, we aimed to explore the mechanisms involved in carbamazepine (CBZ) and microRNA (miR)-20a-5p/ubiquitin-specific peptidase 10 (USP10)/S-phase kinase-associated protein 2 (SKP2) axis in osteoporosis.
METHODS
Human bone marrow mesenchymal stem cells (BMSCs) were treated with different concentrations of CBZ. Knocking down or overexpressing miR-20a-5p, USP10, and SKP2 cell lines were constructed. The expressions of miR-20a-5p, USP10, SKP2, runt-related transcription factor 2 (Runx2), Alkaline phosphatase (ALP), Osterix (Osx), osteocalcin (OCN) and Collagen I were detected with western blot (WB) and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Alizarin Red S (ARS) staining was performed to measure calcium deposition. Dual-luciferase assay and RNA immunoprecipitation (RIP) were applied to verify the binding relationship between miR-20a-5p and USP10. USP10 and SKP2 combination was verified by Co-Immunopurification (Co-IP). The stability of the SKP2 protein was verified by Cycloheximide chase assay.
RESULTS
CBZ could reduce cell activity. ALP activity and ARS staining were enhanced in the osteogenic induction (OM) group. The expressions of Runx2, ALP, Osx, OCN and Collagen I were increased. CBZ reduced miR-20a-5p expressions. Verification experiments showed miR-20a-5p could target USP10. USP10 increased SKP2 stability and promoted SKP2 expression. CBZ regulated miR-20a-5p/USP10/SPK2 and inhibited BMSCs osteogenic differentiation.
CONCLUSIONS
CBZ regulated USP10 through miR-20a-5p to affect the deubiquitination of SKP2 and inhibit osteogenic differentiation, which provided a new idea for osteoporosis treatment.
Topics: Humans; MicroRNAs; Core Binding Factor Alpha 1 Subunit; S-Phase Kinase-Associated Proteins; Osteogenesis; Cells, Cultured; Cell Differentiation; Osteoporosis; Carbamazepine; Alkaline Phosphatase; Collagen; Ubiquitin Thiolesterase
PubMed: 37915040
DOI: 10.1186/s13018-023-04169-7 -
Dental Materials Journal Nov 2023This study aimed to assess the effect of different calcium silicate-based root canal sealers (CSRS) on osteogenic effect in human periodontal ligament cells (hPDLCs)....
This study aimed to assess the effect of different calcium silicate-based root canal sealers (CSRS) on osteogenic effect in human periodontal ligament cells (hPDLCs). hPDLCs were cultured in a medium containing extract of 5 types of CSRS. The specimens were assessed by the cell cytotoxicity test, alkaline phosphatase staining, alizarin red S staining, quantitative real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay. The diluted concentrations of extracted solutions had no significant effect on the viability of hPDLCs. There was a statistically significant difference in the mRNA expression level of bone sialoprotein (BSP), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2) among some groups. The protein expressions of BSP, OCN, and RUNX2 were significantly higher in some groups compared to the control group. The CSRS did not interfere with the osteogenic differentiation of hPDLCs, compared to the control group. CSRS are shown to have biocompatibility and osteogenic differentiation effect on hPDLCs.
Topics: Humans; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Osteogenesis; Calcium Compounds; Cell Differentiation; Periodontal Ligament; Alkaline Phosphatase
PubMed: 37914232
DOI: 10.4012/dmj.2023-048 -
Renal Failure 2023Iguratimod has been shown to promote bone formation and inhibit bone resorption in rheumatoid arthritis patients. We aimed to explore its effect on bone metabolism and...
BACKGROUND
Iguratimod has been shown to promote bone formation and inhibit bone resorption in rheumatoid arthritis patients. We aimed to explore its effect on bone metabolism and vascular calcification (VC) in kidney transplant recipients (KTRs).
METHODS
A analysis was conducted among the subjects in our previous randomized clinical trial (NCT02839941). Forty-three KTRs completing bone metabolism 52 weeks after enrollment were selected for this analysis, among whom 27 patients received VC examinations. In the iguratimod group, iguratimod (25 mg twice daily) was added adjuvant to the traditional triple regimen. At the 52-week follow-up, the following parameters were assessed: serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), osteocalcin, type I collagen N-terminal peptide (NTx), type I collagen C-terminal peptide (CTx), bone mineral density (BMD) of the femoral neck and lumbar spine, coronary artery calcification (CAC) and thoracic aortic calcification (TAC). Bone metabolic and VC indices were compared between the two groups using the independent samples t test and Wilcoxon nonparametric test.
RESULTS
At 52 weeks after enrollment, the iguratimod group had lower osteocalcin ( = 0.010), BALP ( = 0.015), NTx ( = 0.007), CTx ( = 0.012), CAC ( = 0.080) and TAC scores ( = 0.036) than the control group. There was no significant difference in serum calcium, phosphorus, 25-hydroxyvitamin D, iPTH and BMD between the groups. Iguratimod could reduce bone turnover markers (BTMs) at both high and low iPTH levels. The adverse effect of iguratimod was mild and tolerable.
CONCLUSION
Iguratimod is safe, can reduce BTMs and may could attenuate VC in the first year after KT.
Topics: Humans; Collagen Type I; Kidney Transplantation; Calcium; Osteocalcin; Bone Density; Peptides; Parathyroid Hormone; Biomarkers; Minerals; Phosphorus; Bone Remodeling
PubMed: 37905940
DOI: 10.1080/0886022X.2023.2256418