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Nutrients Aug 2021We aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with prognosis, artificial nutrition, circulating osteocalcin, and...
We aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with prognosis, artificial nutrition, circulating osteocalcin, and other serum markers of inflammation and compare them with non-COVID-19 patients. Fifty-two critical patients at the intensive care unit (ICU), 26 with COVID-19 and 26 non-COVID-19, were included. Glycemic control, delivery of artificial nutrition, serum osteocalcin, total and ICU stays, and mortality were recorded. Patients with COVID-19 had higher ICU stays, were on artificial nutrition for longer ( = 0.004), and needed more frequently insulin infusion therapy ( = 0.022) to control stress hyperglycemia. The need for insulin infusion therapy was associated with higher energy ( = 0.001) and glucose delivered through artificial nutrition ( = 0.040). Those patients with stress hyperglycemia showed higher ICU stays (23 ± 17 vs. 11 ± 13 days, = 0.007). Serum osteocalcin was a good marker for hyperglycemia, as it inversely correlated with glycemia at admission in the ICU ( = -0.476, = 0.001) and at days 2 ( = -0.409, = 0.007) and 3 ( = -0.351, = 0.049). In conclusion, hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays. Low circulating osteocalcin was a good marker for stress hyperglycemia.
Topics: Aged; Biomarkers; COVID-19; Critical Care Outcomes; Critical Illness; Female; Humans; Hyperglycemia; Intensive Care Units; Length of Stay; Male; Middle Aged; Osteocalcin; Parenteral Nutrition; Prognosis; SARS-CoV-2
PubMed: 34578888
DOI: 10.3390/nu13093010 -
Experimental and Therapeutic Medicine Feb 2022The present study aimed to investigate whether VEGF was involved in bisphosphonate (BP)-induced apoptosis and differentiation of osteoblasts. Murine MC3T3-E1 osteoblasts...
The present study aimed to investigate whether VEGF was involved in bisphosphonate (BP)-induced apoptosis and differentiation of osteoblasts. Murine MC3T3-E1 osteoblasts were stimulated with zoledronic acid (ZA) for 7 days. VEGF mRNA and protein expression levels were determined via reverse transcription-quantitative PCR and western blot analysis, respectively. Cell viability was evaluated using Cell Counting Kit-8 assay. In addition, the cell apoptotic rate and the expression levels of apoptosis-related proteins were measured using a TUNEL staining kit and western blot analysis, respectively. To evaluate mineralization, cells were stained with alizarin red, while the secretion levels of alkaline phosphatase (ALP) were measured using the corresponding assay kit. Finally, the expression levels of differentiation-related proteins and proteins of the Nod-like receptor family pyrin domain-containing 3 (NLRP3)/caspase 1/gasdermin D (GSDMD) pyroptosis pathway were measured by western blot analysis. VEGF expression level was notably decreased in ZA-stimulated MC3T3-E1 cells. However, the viability of these cells was enhanced following VEGF addition. Furthermore, VEGF attenuated apoptosis, promoted mineralization and increased ALP activity in ZA-stimulated MC3T3-E1 cells. The ZA-mediated decrease in the protein expression of the osteogenic genes osteopontin, osteocalcin and runt-related transcription factor 2 was restored after MC3T3-E1 cell treatment with 10 ng/ml VEGF. The present study demonstrated that VEGF could attenuate BP-induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway.
PubMed: 34970353
DOI: 10.3892/etm.2021.11053 -
Tzu Chi Medical Journal 2023Osteocalcin, a protein from osteoblasts, affects bone mineralization and turnover. This study evaluates the association between fasting serum osteocalcin and bone...
OBJECTIVES
Osteocalcin, a protein from osteoblasts, affects bone mineralization and turnover. This study evaluates the association between fasting serum osteocalcin and bone mineral density (BMD) in renal transplant recipients.
MATERIALS AND METHODS
This study recruited 66 renal transplant recipients. We analyzed blood biochemistry studies from fasting blood samples. The serum osteocalcin levels were measured using a commercial enzyme immunoassay kit. We measure BMD by dual-energy X-ray absorptiometry in lumbar vertebrae (L2-L4). By the World Health Organization classification, we group recipients into three groups: normal, osteopenia, and osteoporosis.
RESULTS
Of the renal transplant recipients, 8 patients (12.1%) were osteoporosis, and 28 patients (42.4%) were osteopenia. From normal to osteoporosis groups, the osteoporosis group has highest serum osteocalcin ( < 0.001), alkaline phosphatase ( = 0.005), lowest body mass index ( = 0.015), and body weight ( = 0.008). Females had lower lumbar BMD than males among recruited renal transplant recipients ( = 0.023). In the multivariate forward stepwise linear regression analysis, body weight (adjusted change = 0.138; = 0.010), and logarithmically transformed osteocalcin (log-osteocalcin; adjusted R change = 0.131; = 0.012) can predict lumbar BMD in the renal transplant recipients.
CONCLUSION
Our study showed that fasting serum osteocalcin concentration was negatively correlated with the lumbar BMD in renal transplant recipients.
PubMed: 37261295
DOI: 10.4103/tcmj.tcmj_55_22 -
Journal of Orthopaedic Surgery and... Oct 2021With the increasing incidence of osteoporosis, vitamin K and calcium have been linked to bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC) in many... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the increasing incidence of osteoporosis, vitamin K and calcium have been linked to bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC) in many studies, but the results of studies of the combined effect of vitamin K and calcium on BMD and UcOC in humans have been inconsistent. We conducted a systematic review of randomized controlled trials to assess the effect of this combination treatment on BMD and UcOC in humans.
METHODS
A search for articles was conducted using PubMed, Embase, and the Cochrane Library database up to March 2021 (no language restrictions). We also reviewed the reference lists of the relevant publications and reviews to locate additional publications. The standard mean difference (SMD) was used as the primary measure of effect size. Our main endpoints were lumbar BMD, femoral neck BMD, hip BMD, total femoral BMD, and UcOC from baseline to end point. We performed subgroup analysis, heterogeneity testing, and assessment of publication bias.
RESULTS
A total of 1346 patients from 10 randomized controlled trials were included in the meta-analysis. The forest plot analysis revealed that vitamin K combined with calcium was associated with a higher lumbar spine BMD compared to controls. The SMD was 0.20 [95% confidence interval (CI): 0.07 to 0.32]. Vitamin K and calcium supplementation led to a significant decrease in UcOC (SMD: - 1.71, 95% CI: - 2.45 to - 0.96). Subgroup analysis showed that vitamin K2 and vitamin K1 had SMDs of 0.30 (95% CI: 0.10 to 0.51) and SMDs of 0.14 (95% CI: - 0.02 to 0.29), and calcium dosages of ≤ 1000 mg/d or > 1000 mg/d had SMDs of 0.19 (95% CI: 0.05 to 0.32) and 0.26 (95% CI: - 0.04 to 0.55).
CONCLUSION
The combination of vitamin K and calcium has a positive effect on lumbar BMD and decreases the level of UcOC. Registration: The protocol for this meta-analysis was registered at the International Prospective Register of Systematic Reviews (CRD42021251825).
Topics: Bone Density; Calcium; Humans; Osteocalcin; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Vitamin K
PubMed: 34649591
DOI: 10.1186/s13018-021-02728-4 -
International Endodontic Journal Mar 2022The pulp contains a resident population of stem cells which can be stimulated to differentiate in order to repair the tooth by generating a mineralized extracellular... (Review)
Review
BACKGROUND
The pulp contains a resident population of stem cells which can be stimulated to differentiate in order to repair the tooth by generating a mineralized extracellular matrix. Over recent decades there has been considerable interest in utilizing in vitro cell culture models to study dentinogenesis, with the aim of developing regenerative endodontic procedures, particularly where some vital pulp tissue remains.
OBJECTIVES
The purpose of this review is to provide a structured oversight of in vitro research methodologies which have been used to study human pulp mineralization processes.
METHOD
The literature was screened in the PubMed database up to March 2021 to identify manuscripts reporting the use of human dental pulp cells to study mineralization. The dataset identified 343 publications initially which were further screened and consequently 166 studies were identified and it was methodologically mined for information on: i) study purpose, ii) source and characterization of cells, iii) mineralizing supplements and concentrations, and iv) assays and markers used to characterize mineralization and differentiation, and the data was used to write this narrative review.
RESULTS
Most published studies aimed at characterizing new biological stimulants for mineralization as well as determining the effect of scaffolds and dental (bio)materials. In general, pulp cells were isolated by enzymatic digestion, although the pulp explant technique was also common. For enzymatic digestion, a range of enzymes and concentrations were utilized, although collagenase type I and dispase were the most frequent. Isolated cells were not routinely characterized using either fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) approaches and there was little consistency in terming cultures as dental pulp cells or dental pulp stem cells. A combination of media supplements, at a range of concentrations, of dexamethasone, ascorbic acid and beta-glycerophosphate, were frequently applied as the basis for the experimental conditions. Alizarin Red S (ARS) staining was the method of choice for assessment of mineralization at 21-days. Alkaline phosphatase assay was relatively frequently applied, solely or in combination with ARS staining. Further assessment of differentiation status was performed using transcript or protein markers, with dentine sialophosphoprotein (DSPP), osteocalcin and dentine matrix protein-1 (DMP -1), the most frequent.
DISCUSSION
While this review highlights variability among experimental approaches, it does however identify a consensus experimental approach.
CONCLUSION
Standardization of experimental conditions and sustained research will significantly benefit endodontic patient outcomes in the future.
Topics: Alkaline Phosphatase; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Pulp; Extracellular Matrix Proteins; Humans; Phosphoproteins; Sialoglycoproteins
PubMed: 35030284
DOI: 10.1111/iej.13684 -
American Journal of Human Biology : the... Aug 2022Ethnic groups differ in prevalence of calcium-related diseases. Differences in the physiology and the endogenous circadian rhythm (CR) of calcium and bone homeostasis...
OBJECTIVES
Ethnic groups differ in prevalence of calcium-related diseases. Differences in the physiology and the endogenous circadian rhythm (CR) of calcium and bone homeostasis may play a role. Thus, we aimed to investigate details of CR pattern in calcium and bone homeostasis in East African Maasai.
METHODS
Ten clinically healthy adult Maasai men and women from Tanzania were examined. Blood samples were collected every 2nd hour for 24 h. Serum levels of total calcium, albumin, parathyroid hormone (PTH), 25(OH)D, creatinine, C-terminal telopeptide (CTX), bone-specific alkaline phosphatase (BSAP), procollagen type 1 N-terminal propeptide (P1NP), and osteocalcin were measured. Circadian patterns were derived from graphic curves of medians, and rhythmicity was assessed with Fourier analysis.
RESULTS
PTH-levels varied over the 24 h exhibiting a bimodal pattern. Nadir level corresponded to 65% of total 24-h mean. CTX and P1NP showed 24-h variations with a morning nadir and nocturnal peak with nadir levels corresponding to 23% and 79% of the 24-h mean, respectively. Albumin-corrected calcium level was held in a narrow range and alterations were corresponding to alterations in PTH. There was no distinct pattern in 24-h variations of 25(OH)D, creatinine, osteocalcin, or BSAP.
CONCLUSIONS
All participants showed pronounced 24-h variations in PTH and bone turnover markers CTX and P1NP. These findings support that Maasai participants included in this study have typical patterns of CR in calcium and bone homeostasis consistent with findings from other ethnic populations.
Topics: Adult; Albumins; Biomarkers; Bone and Bones; Calcium; Circadian Rhythm; Creatinine; Ethnicity; Female; Homeostasis; Humans; Male; Osteocalcin; Parathyroid Hormone; Tanzania
PubMed: 35481615
DOI: 10.1002/ajhb.23756 -
Lipids in Health and Disease Aug 2020Recent studies have investigated the circulating adipocyte fatty acid binding protein (FABP4), nesfatin-1, and osteocalcin (OC) concentrations in women diagnosed with... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Recent studies have investigated the circulating adipocyte fatty acid binding protein (FABP4), nesfatin-1, and osteocalcin (OC) concentrations in women diagnosed with gestational diabetes mellitus (GDM), but the findings prove to be conflicting. The objective of this research was to systematically assess the relationship of circulating levels of above adipokines with GDM.
METHODS
Pubmed, Embase, Web of Science, Cochrane library, OVID, and Scopus were performed to locate articles published up to January 31, 2020. Pooled standard mean differences (SMDs) with 95% confidence intervals (CIs), and 95% predictive intervals (PIs) were calculated by random-effects models to compare levels of adipokines between GDM cases and control groups. Cumulative and single-arm meta-analyses were also performed.
RESULTS
Thirty-one studies comprising 4590 participants were included. No significant differences were found between GDM women and healthy controls in circulating nesfatin-1 levels (4.56 vs. 5.02 ng/mL; SMD = - 0.11, 95% CI -0.61-0.38, 95% PI -1.63-1.41). Nevertheless, circulating FABP4 and OC levels observed in GDM women outnumbered normal controls (FABP4, 23.68 vs. 16.04 ng/mL; SMD = 2.99, 95% CI 2.28-3.69, 95% PI 0.28-5.71; OC, 52.34 vs. 51.04 ng/mL; SMD = 0.68, 95% CI 0.31-1.05, 95% PI -0.48-1.84). The cumulative meta-analysis showed that the SMDs of circulating FABP4 and OC levels had stabilized between the two groups.
CONCLUSIONS
Elevated circulating FABP4 and OC levels were observed in GDM women, but nesfatin-1 levels did not change, the PI of OC crossed the no-effect threshold. The results suggested that FABP4 is more suitable as a biomarker of GDM compared to OC in a future study, which is useful in identifying pregnant women who are likely to develop GDM and providing prompt management strategies.
Topics: Diabetes, Gestational; Fatty Acid-Binding Proteins; Female; Humans; Nucleobindins; Osteocalcin; Pregnancy
PubMed: 32861247
DOI: 10.1186/s12944-020-01365-w -
Frontiers in Cell and Developmental... 2022Bone defects are a global public health problem. However, the available methods for inducing bone regeneration are limited. The application of traditional Chinese herbs...
Bone defects are a global public health problem. However, the available methods for inducing bone regeneration are limited. The application of traditional Chinese herbs for bone regeneration has gained popularity in recent years. β-ecdysterone is a plant sterol similar to estrogen, that promotes protein synthesis in cells; however, its function in bone regeneration remains unclear. In this study, we investigated the function of β-ecdysterone on osteoblast differentiation and bone regeneration and . MC3T3-E1 cells were used to test the function of β-ecdysterone on osteoblast differentiation and bone regeneration . The results of the Cell Counting Kit-8 assay suggested that the proliferation of MC3T3-E1 cells was promoted by β-ecdysterone. Furthermore, β-ecdysterone influenced the expression of osteogenesis-related genes, and the bone regeneration capacity of MC3T3-E1 cells was detected by polymerase chain reaction, the alkaline phosphatase (ALP) test, and the alizarin red test. β-ecdysterone could upregulate the expression of osteoblastic-related genes, and promoted ALP activity and the formation of calcium nodules. We also determined that β-ecdysterone increased the mRNA and protein levels of components of the BMP-2/Smad/Runx2/Osterix pathway. DNA sequencing further confirmed these target effects. β-ecdysterone promoted bone formation by enhancing gene expression of the BMP-2/Smad/Runx2/Osterix signaling pathway and by enrichment biological processes. For experiments, a femoral condyle defect model was constructed by drilling a bone defect measuring 3 mm in diameter and 4 mm in depth in the femoral condyle of 8-week-old Sprague Dawley male rats. This model was used to further assess the bone regenerative functions of β-ecdysterone. The results of micro-computed tomography showed that β-ecdysterone could accelerate bone regeneration, exhibiting higher bone volume, bone surface, and bone mineral density at each observation time point. Immunohistochemistry confirmed that the β-ecdysterone also increased the expression of collagen, osteocalcin, and bone morphogenetic protein-2 in the experiment group at 4 and 8 weeks. In conclusion, β-ecdysterone is a new bone regeneration regulator that can stimulate MC3T3-E1 cell proliferation and induce bone regeneration through the BMP-2/Smad/Runx2/Osterix pathway. This newly discovered function of β-ecdysterone has revealed a new direction of osteogenic differentiation and has provided novel therapeutic strategies for treating bone defects.
PubMed: 35669516
DOI: 10.3389/fcell.2022.883228 -
Frontiers in Bioengineering and... 2021Regenerative endodontic procedures using autologous platelet-rich plasma (PRP) can improve the biologic outcome of treatment. However, its mechanism of action on...
Regenerative endodontic procedures using autologous platelet-rich plasma (PRP) can improve the biologic outcome of treatment. However, its mechanism of action on improving pulp regeneration is not fully elucidated. Autophagy was recently shown to be related to tissue repair and osteogenesis. Therefore, the objective of this study was to investigate the effect of PRP in dental pulp regeneration and to elucidate the role of autophagy involved in this process. Human dental pulp cells (hDPCs) were isolated from healthy dental pulp and co-cultured with an increasing concentration of PRP. Cellular migration and proliferation were determined by scratch assay, transwell assay, and cell-counting kit 8 assay. Osteogenic differentiation was clarified by using alkaline phosphatase staining, alizarin red staining, and real-time polymerase chain reaction (RT-PCR) to measure the gene expression levels of alkaline phosphatase, collagen-1, osteocalcin, dentin matrix protein 1, and dentin sialophosphoprotein. Autophagic bodies were observed by transmission electron microscopy and the expression of autophagy marker light chain 3B (LC3B) was determined by immunofluorescence staining. The mRNA and protein expression level of LC3B and Beclin-1 were quantified by qRT-PCR and western blotting. The effect of PRP on cellular migration, proliferation, and osteogenic differentiation was further investigated in the milieu of autophagy activator, rapamycin, and inhibitor, 3-methyladenine. Results showed that PRP promoted cell migration, proliferation, and osteogenic differentiation. Autophagic bodies were strongly activated and the expression level of LC3B and Beclin-1 was significantly promoted by PRP. Autophagy inhibition suppressed PRP-induced hDPCs migration, proliferation, and osteogenic differentiation, whereas autophagy activator substantially augmented PRP-stimulated migration, proliferation, and differentiation. Taken together, these findings suggested that PRP could effectively promote regenerative potentials associated with autophagy.
PubMed: 34568294
DOI: 10.3389/fbioe.2021.659742 -
Translational Psychiatry May 2024Growing evidence suggests an association between osteocalcin (OCN), a peptide derived from bone and involved in regulating glucose and lipid metabolism, and the risk of...
Growing evidence suggests an association between osteocalcin (OCN), a peptide derived from bone and involved in regulating glucose and lipid metabolism, and the risk of Alzheimer's disease (AD). However, the causality of these associations and the underlying mechanisms remain uncertain. We utilized a Mendelian randomization (MR) approach to investigate the causal effects of blood OCN levels on AD and to assess the potential involvement of glucose and lipid metabolism. Independent instrumental variables strongly associated (P < 5E-08) with blood OCN levels were obtained from three independent genome-wide association studies (GWAS) on the human blood proteome (N = 3301 to 35,892). Two distinct summary statistics datasets on AD from the International Genomics of Alzheimer's Project (IGAP, N = 63,926) and a recent study including familial-proxy AD patients (FPAD, N = 472,868) were used. Summary-level data for fasting glucose (FG), 2h-glucose post-challenge, fasting insulin, HbA1c, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol (TC), and triglycerides were incorporated to evaluate the potential role of glucose and lipid metabolism in mediating the impact of OCN on AD risk. Our findings consistently demonstrate a significantly negative correlation between genetically determined blood OCN levels and the risk of AD (IGAP: odds ratio [OR, 95%CI] = 0.83[0.72-0.96], P = 0.013; FPAD: OR = 0.81 [0.70-0.93], P = 0.002). Similar estimates with the same trend direction were obtained using other statistical approaches. Furthermore, employing multivariable MR analysis, we found that the causal relationship between OCN levels and AD was disappeared after adjustment of FG and TC (IGAP: OR = 0.97[0.80-1.17], P = 0.753; FPAD: OR = 0.98 [0.84-1.15], P = 0.831). There were no apparent instances of horizontal pleiotropy, and leave-one-out analysis showed good stability of the estimates. Our study provides evidence supporting a protective effect of blood OCN levels on AD, which is primarily mediated through regulating FG and TC levels. Further studies are warranted to elucidate the underlying physio-pathological mechanisms.
Topics: Humans; Alzheimer Disease; Osteocalcin; Mendelian Randomization Analysis; Genome-Wide Association Study; Energy Metabolism; Blood Glucose; Polymorphism, Single Nucleotide; Male; Female; Triglycerides; Insulin
PubMed: 38769320
DOI: 10.1038/s41398-024-02924-w