-
Nutrients Dec 2021Osteocalcin, in its non-carboxylated form, has a positive effect on glucose metabolism. Additionally, osteocalcin levels are related to body composition, especially...
Osteocalcin, in its non-carboxylated form, has a positive effect on glucose metabolism. Additionally, osteocalcin levels are related to body composition, especially muscle mass. The relation to the distribution of different adipose tissue types, such as subcutaneous, intermuscular, and visceral adipose tissue, is unclear. This study aimed to investigate associations between serum osteocalcin and the distribution of subcutaneous and intermuscular adipose tissue of the mid-thigh. Furthermore, the influence of different training methods on osteocalcin levels was investigated. We performed adipose tissue quantification of subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT) using MRI measurements of the mid-thigh in 128 volunteers (63 male/65 female). Laboratory analysis included blood lipid panel, serum insulin, adiponectin, and osteocalcin measurements. The main observation was a significant correlation of total serum osteocalcin (TOC) and the distribution of adipose tissue of the mid-thigh (SAT/(SAT + IMAT)) (cc = -0.29/-value = 0.002), as well as the cross-sectional muscle area (MA), increasing with the weekly resistance training duration in males. Additionally, TOC (-value = 0.01) and MA (-value = 0.03) were negatively related to serum insulin. The significant relationship between TOC and SAT/(SAT + IMAT) is a new finding and confirms the negative influence of IMAT on glucose metabolism in a sex-specific approach. We could substantiate this by the negative relation of TOC with serum insulin.
Topics: Adipose Tissue; Adult; Body Composition; Female; Humans; Insulin; Magnetic Resonance Imaging; Male; Middle Aged; Osteocalcin; Sex Factors
PubMed: 35010988
DOI: 10.3390/nu14010112 -
Marine Drugs Feb 2022Fucoidan, a marine-sulfated polysaccharide derived from brown algae, has been recently spotlighted as a natural biomaterial for use in bone formation and regeneration....
Fucoidan, a marine-sulfated polysaccharide derived from brown algae, has been recently spotlighted as a natural biomaterial for use in bone formation and regeneration. Current research explores the osteoinductive and osteoconductive properties of fucoidan-based composites for bone tissue engineering applications. The utility of fucoidan in a bone tissue regeneration environment necessitates a better understanding of how fucoidan regulates osteogenic processes at the molecular level. Therefore, this study designed a fucoidan and polydopamine (PDA) composite-based film for use in a culture platform for periodontal ligament stem cells (PDLSCs) and explored the prominent molecular pathways induced during osteogenic differentiation of PDLSCs through transcriptome profiling. Characterization of the fucoidan/PDA-coated culture polystyrene surface was assessed by scanning electron microscopy and X-ray photoelectron spectroscopy. The osteogenic differentiation of the PDLSCs cultured on the fucoidan/PDA composite was examined through alkaline phosphatase activity, intracellular calcium levels, matrix mineralization assay, and analysis of the mRNA and protein expression of osteogenic markers. RNA sequencing was performed to identify significantly enriched and associated molecular networks. The culture of PDLSCs on the fucoidan/PDA composite demonstrated higher osteogenic potency than that on the control surface. Differentially expressed genes (DEGs) ( = 348) were identified during fucoidan/PDA-induced osteogenic differentiation by RNA sequencing. The signaling pathways enriched in the DEGs include regulation of the actin cytoskeleton and Ras-related protein 1 and phosphatidylinositol signaling. These pathways represent cell adhesion and cytoskeleton organization functions that are significantly involved in the osteogenic process. These results suggest that a fucoidan/PDA composite promotes the osteogenic potential of PDLSCs by activation of critical molecular pathways.
Topics: Actin Cytoskeleton; Alkaline Phosphatase; Cell Adhesion; Cell Differentiation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Humans; Hydrogels; Indoles; Osteocalcin; Osteogenesis; Periodontal Ligament; Polymers; Polysaccharides; Protein Interaction Maps; Stem Cells; Surface Properties; Undaria
PubMed: 35323480
DOI: 10.3390/md20030181 -
Poultry Science Jan 2021The aim of this study was to investigate the effects of osteocalcin (OCN) on fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Thirty 68-week-old White...
Osteocalcin prevents insulin resistance, hepatic inflammation, and activates autophagy associated with high-fat diet-induced fatty liver hemorrhagic syndrome in aged laying hens.
The aim of this study was to investigate the effects of osteocalcin (OCN) on fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Thirty 68-week-old White Plymouth laying hens were randomly assigned into conventional single-bird cages, and the cages were randomly allocated into one of 3 treatments (n = 10): normal diet (ND + vehicle, ND + V), high-fat diet (HFD + vehicle, HFD + V), and HFD + OCN (3 μg/bird, 1 time/2 d, i.m.) for 40 d. At day 30, oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) were performed. At the end of experiment, the hens were euthanized followed by blood collection. The plasma aspartate transaminase (AST), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automatic biochemistry analyzer. Pathological changes in the liver were examined under both light and transmission electron microscopes. The plasma inflammatory factors including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed by ELISA, and the gene expressions of these inflammatory factors in the liver were analyzed by real-time PCR. The level of oxidative stress was evaluated using malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) assay kits, respectively. The results showed that HFD + V hens had more severe liver hemorrhage and fibrosis than ND + V hens (P < 0.05). The ultramicrostructural examination showed that hepatocytes of HFD + V hens exhibited necrotic pyknosis showing great intracellular electron, mitochondrial swelling, shrunk nucleus, and absence of autolysosomes. Osteocalcin mitigated HFD + V-induced pathological changes in aged laying hens. High-fat diet + OCN hens had higher insulin sensitivity; lower liver concentrations of MDA (P = 0.12) but higher GSH-Px (P < 0.05); and lower blood TNF-α concentrations (P < 0.05) and mRNA expressions (P < 0.05) than HFD + V hens. These results suggest OCN functions in preventing the FLHS process in old laying hens through inhibiting excessive energy diet-induced metabolic disorder, oxidative stress, and related pathological damage.
Topics: Animals; Autophagy; Chickens; Diet, High-Fat; Fatty Liver; Female; Inflammation; Insulin Resistance; Liver; Osteocalcin; Poultry Diseases; Random Allocation
PubMed: 33357709
DOI: 10.1016/j.psj.2020.10.022 -
Acta Biochimica Polonica 2017Carboxylated osteocalcin (Gla-OC) contributes to the bone formation, whereas its undercarboxylated form (Glu-OC) takes part in the energy metabolism. In vitro studies...
Carboxylated osteocalcin (Gla-OC) contributes to the bone formation, whereas its undercarboxylated form (Glu-OC) takes part in the energy metabolism. In vitro studies had shown that treatment of osteoblast-like cells with advanced glycation end product-modified bovine serum resulted in reduced synthesis of collagen 1 and osteocalcin. The aim of this study was to find association between Gla-OC and markers of protein glycation, oxidation and nitration, as well as pro-inflammatory and antioxidant defense markers in obese subjects. Non-obese [(body mass index (BMI)<30 kg/m; n=34)] and obese subjects (30
Topics: Adult; Aged; Antioxidants; Biomarkers; Case-Control Studies; Female; Glycation End Products, Advanced; Humans; Kynurenine; Lysine; Male; Middle Aged; Obesity; Osteocalcin; Oxidative Stress; Proteins
PubMed: 28841723
DOI: 10.18388/abp.2017_1627 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2013To assess the effect of topical application of melatonin to the gingiva on salivary fluid concentrations of acid phosphatase, alkaline phosphatase, osteopontin, and...
OBJECTIVES
To assess the effect of topical application of melatonin to the gingiva on salivary fluid concentrations of acid phosphatase, alkaline phosphatase, osteopontin, and osteocalcin.
STUDY DESIGN
Cross-sectional study of 30 patients with diabetes and periodontal disease and 30 healthy subjects. Diabetic patients were treated with topical application of melatonin (1% orabase cream formula) once daily for 20 days and controls with a placebo formulation.
RESULTS
Before treatment with melatonin, diabetic patients showed significantly higher mean salivary levels of alkaline and acid phosphatase, osteopontin and osteocalcin than healthy subjects (P < 0.01). After treatment with melatonin, there was a statistically significant decrease of the gingival index (15.84 ± 10.3 vs 5.6 ± 5.1) and pocket depth (28.3 ± 19.5 vs 11.9 ± 9.0) (P < 0.001). Also, use of melatonin was associated with a significant reduction of the four biomarkers. Changes of salivary acid phosphatase and osteopontin correlated significantly with changes in the gingival index, whereas changes of alkaline phosphatase and osteopontin correlated significantly with changes in the pocket depth.
CONCLUSIONS
Treatment with topical melatonin was associated with an improvement in the gingival index and pocket depth, a reduction in salivary concentrations of acid phosphatase, alkaline phosphatase, osteopontin and osteocalcin.
Topics: Acid Phosphatase; Administration, Topical; Adult; Aged; Alkaline Phosphatase; Cross-Sectional Studies; Diabetes Mellitus; Female; Gingiva; Humans; Male; Melatonin; Middle Aged; Osteocalcin; Osteopontin; Periodontal Diseases; Periodontal Index; Saliva
PubMed: 23524437
DOI: 10.4317/medoral.18832 -
Molecular Medicine Reports Apr 2021Human periodontal ligament stem cells (hPDLSCs) associated with bone regeneration serve an important role in the treatment of periodontal disease. Long non‑coding RNAs...
Human periodontal ligament stem cells (hPDLSCs) associated with bone regeneration serve an important role in the treatment of periodontal disease. Long non‑coding RNAs are involved in the osteogenesis of multiple stem cells and can act as a sponge of microRNAs (miRs). The present study aimed to investigate the interaction between Prader Willi/Angelman region RNA 6 () and miR‑106a‑5p, as well as their influences on the osteogenic differentiation of hPDLSCs. hPDLSCs were isolated and cultured in osteogenic medium (OM) or growth medium (GM) for 7 days prior to transfection with overexpression vector, short hairpin RNA or miR‑106a‑5p mimic. The expression levels of runt‑related transcription factor 2, osteocalcin and bone morphogenetic protein 2 (BMP2) were detected by western blotting and reverse transcription‑quantitative PCR (RT‑qPCR), and the expression levels of , miR‑106a‑5p and alkaline phosphatase (ALP) were determined by RT‑qPCR. ALP activity assays and Alizarin red staining were performed to detect osteogenesis and mineralization, respectively. Luciferase activities of wild‑type and mutant and were assessed by conducting a dual‑luciferase reporter assay. The results indicated that expression was upregulated in OM‑incubated hPDLSCs compared with GM‑incubated hPDLSCs, and overexpression increased the osteogenic differentiation and mineralization of hPDLSCs compared with the corresponding control group. By contrast, miR‑106a‑5p expression was downregulated in OM‑incubated hPDLSCs compared with GM‑incubated hPDLSCs. acted as a sponge of miR‑106a‑5p and overexpression promoted the osteogenesis of miR‑106a‑5p mimic‑transfected hPDLSCs. BMP2 was predicted as a target gene of miR‑106a‑5p. Collectively, the results indicated that displayed a positive influence on the osteogenic differentiation of hPDLSCs. The results of the present study demonstrated that the /miR‑106a‑5p interaction network may serve as a potential regulatory mechanism underlying hPDLSCs osteogenesis.
Topics: Alkaline Phosphatase; Blotting, Western; Bone Morphogenetic Protein 2; Cell Differentiation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Humans; MicroRNAs; Osteocalcin; Osteogenesis; Periodontal Ligament; RNA, Long Noncoding; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells
PubMed: 33576453
DOI: 10.3892/mmr.2021.11907 -
Disease Models & Mechanisms Oct 2016Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap), is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse...
Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap), is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap) gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA), glucose tolerance testing (GTT), insulin tolerance testing (ITT), microcomputed tomography (µCT), and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research.
Topics: Absorptiometry, Photon; Alleles; Amino Acid Sequence; Animals; Base Sequence; Biomechanical Phenomena; Body Composition; CRISPR-Cas Systems; Cancellous Bone; Femur; Founder Effect; Genetic Techniques; Glucose Tolerance Test; INDEL Mutation; Insulin; Male; Models, Animal; Osteocalcin; Rats; Species Specificity; X-Ray Microtomography
PubMed: 27483347
DOI: 10.1242/dmm.025247 -
Medicina (Kaunas, Lithuania) May 2024: Brachial-ankle pulse wave velocity (baPWV) is an established independent risk factor for cardiovascular events, cardiovascular mortality, and all-cause mortality....
: Brachial-ankle pulse wave velocity (baPWV) is an established independent risk factor for cardiovascular events, cardiovascular mortality, and all-cause mortality. Osteocalcin (OC) is recognized to be associated with vascular function. The present study assessed the correlation between serum OC levels and peripheral arterial stiffness (PAS) measured through baPWV in hypertensive patients. : Fasting blood samples were collected from 120 hypertensive participants. The serum total OC levels were measured using a commercial enzyme-linked immunosorbent assay kit, whereas the baPWV device was used to detect PAS. The PAS group had left or right baPWV > 18.0 m/s. : Among the hypertensive patients, 24 (20.0%) were classified into the PAS group. The PAS group exhibited a significantly older age ( = 0.011), higher prevalence of diabetes ( = 0.010), systolic blood pressure ( = 0.019), levels of serum fasting glucose ( = 0.003), blood urea nitrogen ( = 0.024), creatinine ( = 0.004), C-reactive protein ( = 0.007), OC ( = 0.002), and lower estimated glomerular filtration rate ( = 0.004) than the non-PAS group. Age (odds ratio [OR]: 1.076, 95% CI: 1.004-1.153, = 0.037) and serum OC level (OR: 1.797, 95% confidence interval (CI): 1.077-3.000, = 0.025) were independent factors linked to PAS in hypertensive patients in the multivariate logistic regression analysis. : Serum OC levels and older age are positively associated with PAS in hypertensive patients.
Topics: Humans; Vascular Stiffness; Male; Female; Middle Aged; Hypertension; Biomarkers; Osteocalcin; Aged; Pulse Wave Analysis; Ankle Brachial Index; Risk Factors; Adult
PubMed: 38793018
DOI: 10.3390/medicina60050835 -
Journal of Bone and Mineral Research :... Sep 2021Recent advances indicate that bone and energy metabolism are closely related. However, little direct evidence on causality has been provided in humans. We aimed to... (Meta-Analysis)
Meta-Analysis
Recent advances indicate that bone and energy metabolism are closely related. However, little direct evidence on causality has been provided in humans. We aimed to assess the association of three bone-related biomarkers-25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and osteocalcin (OCN)-with several metabolic phenotypes and investigate any causal relevance to the associations using a Mendelian randomization (MR) study. Serum 25OHD, PTH, and total OCN were measured at baseline in 5169 eligible Chinese participants in Changfeng study. Partial correlation and bivariate GREML analysis were used to estimate phenotypic and genetic correlations, respectively. Multiple linear regression and logistic regression were used to assess linear associations. Genomewide association analysis (GWAS) was performed. Bidirectional two-sample MR analyses were conducted to examine causal relationships between OCN and body mass index (BMI), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), glycated hemoglobin A1c (HbA1c), and type 2 diabetes (T2DM), using our GWAS result of OCN and GWAS statistics from Biobank Japan project (BBJ) and the largest meta-analysis of T2DM GWAS in East Asian population. Circulating OCN was significantly associated with higher DBP and HDL-C and decreased TG, blood glucose level, insulin resistance, liver fat content, bone mineral density, BMI, and a favorable body fat distribution pattern. GWAS identified one novel serum PTH locus and two novel serum OCN loci, explaining 0.81% and 1.98% of variances of PTH and OCN levels, respectively. MR analysis suggested a causal effect of T2DM on lower circulating OCN concentration (causal effect: -0.03; -0.05 to -0.01; p = 0.006 for T2DM_BBJ and -0.03; -0.05 to -0.01; p = 0.001 for T2DM_EAS). These findings indicate that T2DM might impact bone remodeling and provide a resource for understanding complex relationships between osteocalcin and metabolic (and related) traits in humans. © 2021 American Society for Bone and Mineral Research (ASBMR).
Topics: Bone Density; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Osteocalcin
PubMed: 33956999
DOI: 10.1002/jbmr.4330 -
Journal of Bone and Mineral Research :... Apr 1993The high-resolution, postembedding protein A-gold immunocytochemical technique was used to visualize the distribution of two noncollagenous bone proteins, osteopontin...
The high-resolution, postembedding protein A-gold immunocytochemical technique was used to visualize the distribution of two noncollagenous bone proteins, osteopontin (OPN) and osteocalcin (OC), and two plasma proteins, alpha 2HS-glycoprotein (alpha 2HS-GP) and albumin (ALB), in sections of Lowicryl K4M-embedded rat tibial and alveolar bone. In the primary spongiosa of the metaphysis, a seam of organic material (lamina limitans) that labeled intensely with OPN and OC antibodies was observed at the bone/calcified cartilage interface just below the zone of vascular invasion of the growth plate. With deposition of bone matrix proper by osteoblasts in this region and its subsequent mineralization, extensive areas of bone were heavily labeled with anti-OPN, anti-OC, and anti-alpha 2HS-GP antibodies, where the majority of gold particles were associated with amorphous, electron-dense patches of organic material throughout the mineralized bone. In the unmineralized osteoid, substantially less labeling was observed, and where occasional mineralization loci were dispersed throughout the osteoid layer, these sometimes showed a concentration of gold particles. ALB labeling, on the other hand, was moderate and generally diffuse throughout the mineralized bone matrix and the osteoid. In alveolar bone, labeling patterns were generally similar to those found in tibial bone. Particularly striking in alveolar bone, however, was an intense anti-OPN labeling of (1) the lamina limitans at cell-lined bone surfaces, including that surrounding cell processes and osteocytes, (2) cement (reversal, resting) lines, and (3) the perilacumar matrix of some osteocytes. In summary, these data suggest that certain plasma proteins, such as alpha 2HS-GP, interact with bone matrix proteins, such as OPN and OC, at sites of tissue mineralization and that the presence of OPN in mineralized bone and at bone surfaces (lamina limitans) and cement lines has a multifunctional role, including regulation of mineralization and mediation of cell dynamics during endochondral and intramembranous bone modeling and remodeling.
Topics: Animals; Blood Proteins; Bone Density; Bone and Bones; Fibronectins; Immunohistochemistry; Male; Microscopy, Electron; Osteocalcin; Osteopontin; Rats; Rats, Wistar; Serum Albumin; Sialoglycoproteins; Specimen Handling
PubMed: 8475798
DOI: 10.1002/jbmr.5650080413