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CNS Neuroscience & Therapeutics Dec 2023As the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to...
AIMS
As the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone-derived hormone osteocalcin has been reported to be necessary to prevent anxiety-like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin.
METHODS
Menopausal mouse model was induced by intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light-dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co-localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis-related proteins.
RESULTS
The VCD mice showed obvious anxiety-like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL-2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons.
CONCLUSION
Exercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD-induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise.
Topics: Humans; Mice; Animals; Female; Osteocalcin; Neuroprotection; Bromodeoxyuridine; Anxiety; Menopause; Hippocampus; Neurogenesis
PubMed: 37402694
DOI: 10.1111/cns.14324 -
Journal of Bone and Mineral Research :... Feb 2020Arterial calcification is an important hallmark of cardiovascular disease and shares many similarities with skeletal mineralization. The bone-specific protein...
Arterial calcification is an important hallmark of cardiovascular disease and shares many similarities with skeletal mineralization. The bone-specific protein osteocalcin (OCN) is an established marker of vascular smooth muscle cell (VSMC) osteochondrogenic transdifferentiation and a known regulator of glucose metabolism. However, the role of OCN in controlling arterial calcification is unclear. We hypothesized that OCN regulates calcification in VSMCs and sought to identify the underpinning signaling pathways. Immunohistochemistry revealed OCN co-localization with VSMC calcification in human calcified carotid artery plaques. Additionally, 3 mM phosphate treatment stimulated OCN mRNA expression in cultured VSMCs (1.72-fold, p < 0.001). Phosphate-induced calcification was blunted in VSMCs derived from OCN null mice (Ocn ) compared with cells derived from wild-type (WT) mice (0.37-fold, p < 0.001). Ocn VSMCs showed reduced mRNA expression of the osteogenic marker Runx2 (0.51-fold, p < 0.01) and the sodium-dependent phosphate transporter, PiT1 (0.70-fold, p < 0.001), with an increase in the calcification inhibitor Mgp (1.42-fold, p < 0.05) compared with WT. Ocn VSMCs also showed reduced mRNA expression of Axin2 (0.13-fold, p < 0.001) and Cyclin D (0.71 fold, p < 0.01), markers of Wnt signaling. CHIR99021 (GSK3β inhibitor) treatment increased calcium deposition in WT and Ocn VSMCs (1 μM, p < 0.001). Ocn VSMCs, however, calcified less than WT cells (1 μM; 0.27-fold, p < 0.001). Ocn VSMCs showed reduced mRNA expression of Glut1 (0.78-fold, p < 0.001), Hex1 (0.77-fold, p < 0.01), and Pdk4 (0.47-fold, p < 0.001). This was accompanied by reduced glucose uptake (0.38-fold, p < 0.05). Subsequent mitochondrial function assessment revealed increased ATP-linked respiration (1.29-fold, p < 0.05), spare respiratory capacity (1.59-fold, p < 0.01), and maximal respiration (1.52-fold, p < 0.001) in Ocn versus WT VSMCs. Together these data suggest that OCN plays a crucial role in arterial calcification mediated by Wnt/β-catenin signaling through reduced maximal respiration. Mitochondrial dynamics may therefore represent a novel therapeutic target for clinical intervention. © 2019 American Society for Bone and Mineral Research.
Topics: Animals; Cells, Cultured; Glucose; Mice; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Osteocalcin; Vascular Calcification; Wnt Signaling Pathway
PubMed: 31596966
DOI: 10.1002/jbmr.3888 -
Diabetes/metabolism Research and Reviews Jan 2020
Topics: Adaptor Proteins, Signal Transducing; Cardiovascular Diseases; Humans; Osteocalcin; Prognosis
PubMed: 31600861
DOI: 10.1002/dmrr.3217 -
Biochemical and Biophysical Research... Dec 2022The secretions of osteocalcin and bone morphogenetic protein 2 (BMP2) from living osteoblastic cells were visualized for the first time using a method of video-rate...
The secretions of osteocalcin and bone morphogenetic protein 2 (BMP2) from living osteoblastic cells were visualized for the first time using a method of video-rate bioluminescence imaging. The fusion proteins with Gaussia luciferase (GLase) for mouse osteocalcin and BMP2 (OC-GLase and BMP2-GLase, respectively) expressed in osteoblastic MC3T3-E1 cells were correctly processed and secreted. In the video images of exocytotic secretion, the luminescence spots of OC-GLase and BMP2-GLase disappeared rapidly and gradually, respectively, indicating different manners of these proteins in diffusion. Notably, a deletion mutant of BMP2 (Δ3BMP2-GLase) lacking three basic amino acid residues in the N-terminal region for binding to heparan sulfate showed rapidly disappearing luminescence spots. In our imaging conditions, the half-life of luminescence for the spots of Δ3BMP2-GLase (1.61 ± 0.20 s) was similar to that of OC-GLase (1.22 ± 0.14 s) but not to that of BMP2-GLase (4.31 ± 0.41 s). These results suggest that, in contrast to osteocalcin, the diffusion of BMP2 from cells occurred slowly after exocytosis. Thus, our bioluminescence imaging method is useful to study the diffusion properties of secreted proteins in exocytosis.
Topics: Mice; Animals; Osteocalcin; Bone Morphogenetic Protein 2; Luciferases; Cell Communication; Cell Line; Osteoblasts; Cell Differentiation
PubMed: 36279682
DOI: 10.1016/j.bbrc.2022.10.042 -
Endocrine Mar 2018In the last few years, bone has been recognized as an endocrine organ that modulates glucose metabolism by secretion of osteocalcin, an osteoblast-specific hormone, that...
PURPOSE
In the last few years, bone has been recognized as an endocrine organ that modulates glucose metabolism by secretion of osteocalcin, an osteoblast-specific hormone, that influences fat deposition and blood sugar levels. To date, however, very few in vitro models have been developed to investigate, at the molecular levels, the relationship between glucose, insulin and osteocalcin. This study aims at covering this gap.
METHODS
We studied osteogenic differentiation, osteocalcin gene expression, and osteblast-mediated insulin secretion, using cultured MG-63 human osteoblast-like cells that underwent glucotoxicity and insulin resistance. In addition, we investigated whether a correlation existed between hyperglycemia and/or insulin resistance and total osteocalcin serum concentrations in patients.
RESULTS
While insulin and low glucose increased osteocalcin gene expression, disruption of insulin signaling in MG-63 osteoblasts and high glucose concentration in cell culture medium decreased osteocalcin gene transcription and reduced osteogenic differentiation. Concomitantly, insulin secretion was significantly impaired in rat INS-1 β-cells treated with conditioned medium from insulin resistant MG-63 cells or cells exposed to high glucose concentrations. Also, chronic hyperglycemia, but not insulin resistance, inversely correlated with circulating osteocalcin levels in patients.
CONCLUSION
Our results further support the existence of an endocrine axis between bone, where osteocalcin is produced, and pancreatic β-cells, and add new insights into the molecular details of this relationship. These findings may contribute to the understanding of osteocalcin regulation and its role in metabolism.
Topics: Cell Differentiation; Cell Line; Gene Expression Regulation; Glucose; Humans; Insulin; Insulin Resistance; Osteoblasts; Osteocalcin; Phosphorylation
PubMed: 28866834
DOI: 10.1007/s12020-017-1396-0 -
PloS One 2015To investigate whether total osteocalcin (tOC), uncarboxylated osteocalcin (ucOC) and percentage of uncarboxylated osteocalcin (%ucOC) are associated with the risk of...
OBJECTIVE
To investigate whether total osteocalcin (tOC), uncarboxylated osteocalcin (ucOC) and percentage of uncarboxylated osteocalcin (%ucOC) are associated with the risk of type 2 diabetes.
METHODS
This nested case control study included 1,635 participants, 833 incident diabetes cases and 802 non-diabetic control participants, aged 21-70 years from the EPIC-NL cohort. Baseline concentrations of tOC, ucOC and %ucOC were assessed. During 10 years of follow-up, diabetes cases were self-reported and verified against information from general practitioners or pharmacists. The association between the different forms of osteocalcin and diabetes risk was assessed with logistic regression adjusted for diabetes risk factors (waist circumference, age, sex, cohort, smoking status, family history of diabetes, hypertension, alcohol intake, physical activity and education) and dietary factors (total energy intake and energy adjusted intake of fat, fiber, protein and calcium).
RESULTS
TOC concentration was not associated with diabetes risk, with an odds ratio (OR) of 0.97 (0.91-1.03) for each ng/ml increment after adjustment for diabetes risk factors and dietary factors. No association between ucOC and %ucOC and the risk of diabetes was observed either. In sex stratified analyses (P interaction = 0.07), higher %ucOC tended to be associated with an increased risk of type 2 diabetes in a multivariable model in women (OR 1.05 for each increment of 5% ucOC (1.00-1.11), Ptrend = 0.08), but not in men (OR 0.96 for each increment of 5% ucOC (0.88-1.04)). When waist circumference was replaced by body mass index, none of the osteocalcin forms were associated with the risk of type 2 diabetes in the final model among both women and men.
CONCLUSIONS
Available evidence suggests that tOC, ucOC and %ucOC are each not associated with the risk of type 2 diabetes. However, more large-scale cohort studies are needed to clarify the presence of any association between the different forms of osteocalcin and the risk of type 2 diabetes.
Topics: Adult; Aged; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Osteocalcin; Prospective Studies; Risk Factors; Surveys and Questionnaires; Young Adult
PubMed: 26418005
DOI: 10.1371/journal.pone.0138693 -
FEBS Letters Jun 2023An acidic environment in bone is essential for bone metabolism and the production of decarboxylated osteocalcin, which functions as a regulatory hormone of glucose...
An acidic environment in bone is essential for bone metabolism and the production of decarboxylated osteocalcin, which functions as a regulatory hormone of glucose metabolism. Here, we describe the high-resolution X-ray crystal structure of decarboxylated osteocalcin under acidic conditions. Decarboxylated osteocalcin at pH 2.0 retains the α-helix structure of native osteocalcin with three γ-carboxyglutamic acid residues at neutral pH. This implies that decarboxylated osteocalcin is stable under an acidic environment in bone. In addition, site-directed mutagenesis revealed that Glu17 and Glu21 are important for the adiponectin-inducing activity of decarboxylated osteocalcin. These findings suggest that the receptor of decarboxylated osteocalcin responds to the negative charge in helix 1 of osteocalcin.
Topics: Osteocalcin; Adiponectin; Bone and Bones; 1-Carboxyglutamic Acid
PubMed: 36976525
DOI: 10.1002/1873-3468.14618 -
Nigerian Journal of Clinical Practice Apr 2023Piezocision, a minimally invasive surgical procedure, has been used to accelerate tooth movement'' is appropriate as a background to the abstract section. (Randomized Controlled Trial)
Randomized Controlled Trial
Osteocalcin and cross-linked C-terminal telopeptide of type I collagen in gingival crevicular fluid during piezocision accelerated orthodontic tooth movement: A randomized split-mouth study.
BACKGROUND
Piezocision, a minimally invasive surgical procedure, has been used to accelerate tooth movement'' is appropriate as a background to the abstract section.
AIM
The aim of this randomized split-mouth study was to evaluate gingival crevicular fluid (GCF) osteocalcin (OC) and type I collagen cross-linked C-terminal telopeptide (ICTP) levels during canine distalization with and without piezocision acceleration.
MATERIAL AND METHODS
Fifteen systemically healthy subjects (M:F 7:8, 16.27 ± 1.14 years) requiring extraction of maxillary first premolars before retraction of canines were included in the study. Piezocisions were randomly carried out on one of the maxillary canines while bilateral canines served as controls. Canine distalization was conducted using closed-coil springs applying a force of 150 g/side by using miniscrews as anchorage. GCF sampling was performed from maxillary canine mesial and distal sites at baseline, 1, 7, 14, and 28 days. The GCF levels of OC and ICTP were detected by enzyme-linked immunosorbent assay (ELISA). The rate of tooth movement was evaluated at 2-week intervals.
RESULTS
The amounts of canine distalization from baseline to 14 and 28 days in the piezocision group were significantly higher than the control group (P < 0.05). The GCF OC level of the piezocision group on the tension side and the ICTP level of the same group on the compression side were higher than the respective sides of the control group on day 14 (P < 0.05).
CONCLUSIONS
Piezocision was found to be an effective treatment procedure for accelerating canine distalization accompanied by increased levels of OC and ICTP.
Topics: Collagen Type I; Gingival Crevicular Fluid; Mouth; Osteocalcin; Tooth Movement Techniques; Humans; Male; Female; Adolescent
PubMed: 37203112
DOI: 10.4103/njcp.njcp_539_22 -
Journal of Cellular Physiology Apr 2021Undercarboxylated osteocalcin (ucOC) improves glucose metabolism; however, its effects on endothelial cell function are unclear. We examined the biological effect of...
Undercarboxylated osteocalcin (ucOC) improves glucose metabolism; however, its effects on endothelial cell function are unclear. We examined the biological effect of ucOC on endothelial function in animal models ex vivo and human cells in vitro. Isometric tension and immunohistochemistry techniques were used on the aorta of male New Zealand white rabbits and cell culture techniques were used on human aortic endothelial cells (HAECs) to assess the effect of ucOC in normal and high-glucose environments. Overall, ucOC, both 10 and 30 ng/ml, did not significantly alter acetylcholine-induced blood vessel relaxation in rabbits (p > .05). UcOC treatment did not cause any significant changes in the immunoreactivity of cellular signalling markers (p > .05). In HAEC, ucOC did not change any of the assessed outcomes (p > .05). UcOC has no negative effects on endothelial function which is important to reduce the risks of off target adverse effects if it will be used as a therapeutic option for metabolic disease in the future.
Topics: Animals; Aorta, Abdominal; Cells, Cultured; Endothelial Cells; Glucose; Humans; Male; Osteocalcin; Rabbits; Vasodilation; Vasodilator Agents
PubMed: 32936958
DOI: 10.1002/jcp.30048 -
Journal of Trace Elements in Medicine... Jul 2018The relationship between daily boron intake and osteocalcin-mediated osteoporosis was studied in boron-exposed postmenopausal women. It is known that boron and...
The relationship between daily boron intake and osteocalcin-mediated osteoporosis was studied in boron-exposed postmenopausal women. It is known that boron and osteocalcin are important in bone metabolism, however the effect of boron in bone metabolism has not been fully discovered. The study was performed on 53 postmenopausal women aged 55-60 living in parts of Balikesir, Turkey, where the subjects are naturally exposed to high (≥1 mg/L) or low (<1 mg/L) boron concentration in drinking water. 24-h urine samples were collected from all participants and creatinine clearance was detected. Boron intake levels of the subjects whose clearance levels were between 80-124 mL/min were measured by inductively coupled plasma-optical emission spectrometry (ICP-OES) in urine samples. Serum osteocalcin levels of the subjects were measured by osteocalcin enzyme-linked immunosorbent assay (ELISA) kit. Osteocalcin polymorphism rs1800247 was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serum osteocalcin levels in boron-exposed postmenopausal women were significantly higher than that of control group (P ≤ 0.05) and the correlation between the serum osteocalcin level and rs1800247 polymorphism was not significant in both groups (P > 0.05). The differences in the distribution of osteocalcin genotypes and alleles in postmenopausal women were not significant between the boron exposed and the control groups (P > 0.05). Serum osteocalcin level in the CC genotype was significantly higher compared to the TC genotype in boron-exposed group (P ≤ 0.05). Our study suggests that daily boron intake of 1 mg/L may affect bone metabolism in postmenopausal women positively.
Topics: Boron; Female; Humans; Middle Aged; Minerals; Osteocalcin; Osteoporosis, Postmenopausal; Polymorphism, Genetic
PubMed: 29773193
DOI: 10.1016/j.jtemb.2018.03.005