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Medical Science Monitor : International... Mar 2020BACKGROUND Osteoblast differentiation is a critical process to maintain the stability of the bone homeostasis. Zingerone, 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (ZG),...
BACKGROUND Osteoblast differentiation is a critical process to maintain the stability of the bone homeostasis. Zingerone, 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (ZG), isolated from ginger, performs a wide range of biological functions in human diseases. The objective of this paper was to clarify the role of ZG in human bone mesenchymal stem cells (hBMSCs) and associated mechanisms of ZG promoting osteoblast differentiation. MATERIAL AND METHODS The cytotoxicity of ZG was detected by MTT assay. The expression levels of miR-200c-3p, smad7, and osteoblast differentiation markers (alkaline phosphatase [ALP], osteocalcin [OC], osterix [OSX] and runt-related transcription factor 2 [RUNX2]) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of smad7, ALP, OC, OSX, and RUNX2 were quantified by western blot analysis. The target mRNAs were predicted by bioinformatics tools TargetScan. The interaction between miR-200c-3p and smad7 was verified by luciferase reporter assay and RIP assay. RESULTS ZG was nontoxic to hBMSCs, and it accelerated osteoblast differentiation by inducing the expression of ALP, OC, OSX, and RUNX2. MiR-200c-3p was upregulated, but smad7 was downregulated in hBMSCs treated with ZG at different concentrations at different periods. Besides, miR-200c-3p positively regulated the expression of ALP, OC, OSX, and RUNX2 in ZG-induced hBMSCs. Moreover, miR-200c-3p targeted smad7 and strengthened the expression of ALP, OC, OSX, and RUNX2 in ZG-induced hBMSCs by downregulating smad7. CONCLUSIONS ZG contributed to osteoblast differentiation via miR-200c-3p/smad7 regulatory axis by promoting the expression of ALP, OC, OSX, and RUNX2 in hBMSCs.
Topics: Alkaline Phosphatase; Cell Differentiation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Guaiacol; Humans; Mesenchymal Stem Cells; MicroRNAs; Osteoblasts; Osteocalcin; Osteogenesis; Smad7 Protein; Sp7 Transcription Factor
PubMed: 32146478
DOI: 10.12659/MSM.919309 -
Physiological Research Sep 2020There has been increasing evidence in recent years for the hypothesis of bones as endocrine organs. Osteocalcin, long considered just a marker of new bone formation, is...
There has been increasing evidence in recent years for the hypothesis of bones as endocrine organs. Osteocalcin, long considered just a marker of new bone formation, is now seen as the first hormone produced by bones, and seems to be associated with regulating glucose metabolism and reproduction. The aim of this work was to monitor changes of osteocalcin in reaction to hypoglycemia, and determine if there are differences in such reactions between the sexes. The study included 61 healthy probands with physiological calciophosphate metabolism (30 men and 31 women). We applied to each of them an insulin tolerance test, and then monitored levels of undercarboxylated osteocalcin and reactions to hypoglycemia at regular time intervals. We found differences in the reaction to hypoglycemia between the sexes. In men there was a significant decline in undercarboxylated osteocalcin between the 30 and 40 min (p<0.0015), which reflects a reaction to a glycemic decline between 25-30 min, followed by reversal. Low undercarboxylated osteocalcin in men lasted up to 90 min, after which they returned to levels before the test. In women we did not find any significant changes in undercarboxylated osteocalcin levels. Changes in undercarboxylated osteocalcin induced by hypoglycemia indicate a relationship between bones and glucose metabolism. There was an interesting difference between the sexes. However, a definitive conclusion about the role of osteocalcin in human metabolism will require numerous future studies.
Topics: Adult; Biomarkers; Bone and Bones; Female; Humans; Hypoglycemia; Male; Osteocalcin; Sex Factors
PubMed: 33094629
DOI: 10.33549/physiolres.934520 -
The Journal of Clinical Endocrinology... Mar 2009Osteocalcin has been reported to contribute to the regulation of glucose tolerance and insulin secretion and sensitivity in experimental animals.
CONTEXT
Osteocalcin has been reported to contribute to the regulation of glucose tolerance and insulin secretion and sensitivity in experimental animals.
OBJECTIVE
Our objective was to examine the association between serum osteocalcin concentration and markers of dysmetabolic phenotype using data from a completed clinical trial in adults age 65 and older [n = 380, mean age 71 yr, body mass index (BMI) 26.9 kg/m(2), 5% with diabetes].
RESEARCH DESIGN AND METHODS
In cross-sectional analyses (baseline data), we estimated the associations of serum osteocalcin and urine N-telopeptide with markers of metabolic phenotype including fasting plasma glucose (FPG) (primary outcome), fasting insulin, insulin sensitivity estimated by homeostasis model assessment for insulin resistance, plasma high-sensitivity C-reactive protein, IL-6, and measures of adiposity (BMI and body fat) (secondary outcomes) after multivariate adjustment for potential confounders. In prospective analysis (placebo arm), we estimated the associations of osteocalcin and N-telopeptide with change in the primary outcome, FPG, over a 3-yr period.
RESULTS
In cross-sectional analyses, serum osteocalcin concentration was inversely associated with FPG (P = 0.01), fasting insulin (P = 0.006), homeostasis model assessment for insulin resistance (P = 0.002), high-sensitivity C-reactive protein (P = 0.01), IL-6 (P = 0.02), BMI (P < 0.001), and body fat (P < 0.001). When participants were divided into tertiles by serum osteocalcin, mean FPG was 97.1 vs. 104.8 mg/dl in the highest vs. lowest osteocalcin tertile, respectively (P < 0.01). In prospective analyses, exposure to higher osteocalcin levels during follow-up was associated with a significantly lower rise in FPG at 3 yr. Urine N-telopeptide was not associated with any marker of metabolic phenotype.
CONCLUSIONS
Serum osteocalcin concentration was inversely associated with blood markers of dysmetabolic phenotype and measures of adiposity. Our findings should be considered hypothesis generating, and they need to be replicated in human studies designed to test the hypothesis that osteocalcin affects metabolism.
Topics: Adiposity; Aged; Biomarkers; Blood Glucose; Body Mass Index; Bone Remodeling; Collagen Type I; Cross-Sectional Studies; Energy Metabolism; Female; Humans; Insulin Resistance; Male; Osteocalcin; Peptides; Phenotype
PubMed: 19088165
DOI: 10.1210/jc.2008-1422 -
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 -
International Journal of Environmental... Aug 2022Oral dysfunction is related to long-term cares including activities of daily living. The objective of this study was to determine the association between oral function...
BACKGROUND
Oral dysfunction is related to long-term cares including activities of daily living. The objective of this study was to determine the association between oral function and the bone-related physiological substances osteocalcin (OC) and insulin-like growth factor-1 (IGF-1).
METHODS
The study participants were 139 community-dwelling older people in Japan. Evaluation of oral dysfunction was based on subjective judgment by each participant. Blood analysis included OC, IGF-1, and albumin.
RESULTS
Univariate and multiple logistic analyses showed that IGF-1 was significantly associated with a "decline in masticatory function" ( = 0.0074 and = 0.0308, respectively). Receiver operating characteristic curve analysis of IGF-1 levels revealed a threshold score of 108 ng/mL ( < 0.01) for discriminating a "decline in masticatory function". Logistic regression analysis revealed that participants with an IGF-1 level ≤108 ng/mL had an odds ratio of 4.31 ( < 0.05) for a "decline in masticatory function". No significant association was found between the OC level and oral dysfunction.
CONCLUSIONS
These results suggest a possible relationship between lower serum IGF-1 levels and a decline in masticatory dysfunction in community-dwelling older people.
Topics: Activities of Daily Living; Aged; Cross-Sectional Studies; Humans; Independent Living; Insulin-Like Growth Factor I; Japan; Mastication; Oral Health; Osteocalcin
PubMed: 36078393
DOI: 10.3390/ijerph191710677 -
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 -
European Review For Medical and... Mar 2024Uncarboxylated osteocalcin is an important osteocalcin enzyme found in the bloodstream and is a crucial protein for maintaining calcium binding in bones, controlling...
OBJECTIVE
Uncarboxylated osteocalcin is an important osteocalcin enzyme found in the bloodstream and is a crucial protein for maintaining calcium binding in bones, controlling blood sugar levels, and balancing body minerals.
PATIENTS AND METHODS
Due to the lack of data, the current study intends to investigate the relationship between uncarboxylated osteocalcin levels and DM-II in Saudi patients. For 138 patients, case-control research was conducted in 2021-2023, with 69 type II diabetes mellitus patients and 69 matching healthy control participants. An enzyme immunoassay kit was used to quantify the levels of uncarboxylated osteocalcin in fasting blood samples, and an automated analyzer evaluated Hb1Ac, fasting blood glucose, enzymes, electrolytes, lipid, and kidney profiles. Data processing and analysis were carried out using GraphPad Prism statistical software.
RESULTS
According to our study, patients with type II diabetes mellitus had considerably lower levels of uncarboxylated osteocalcin than healthy controls. According to the correlation analysis, uncarboxylated osteocalcin and fasting blood sugar had a negative relationship. In the overweight BMI group, uncarboxylated osteocalcin was considerably higher in control subjects.
CONCLUSIONS
We concluded that, in Saudi type II diabetes mellitus patients, the compromised glucose level is associated with diminished serum uncarboxylated osteocalcin. This study has limitations, such as a small sample size and only measuring the uncarboxylated form of plasma osteocalcin. Future research is needed to understand how anti-diabetic drugs affect undercarboxylated osteocalcin's effect on metabolic control and provide more efficient techniques and resources in diabetes and osteoporosis prevention and care.
Topics: Humans; Blood Glucose; Diabetes Mellitus, Type 2; Osteocalcin; Body Mass Index; Saudi Arabia
PubMed: 38497883
DOI: 10.26355/eurrev_202403_35615 -
Journal of Medicine and Life Jun 2013Lately, the in vitro and in vivo studies on serotonin metabolism pointed their influence in bone health. In addition, there are no particular recommendations in...
INTRODUCTION
Lately, the in vitro and in vivo studies on serotonin metabolism pointed their influence in bone health. In addition, there are no particular recommendations in performing the serum serotonin assessment in order to evaluate the skeletal status. Aim. We aimed to correlate the bone turnover markers and lumbar bone mineral density (BMD) with serotonin.
MATERIAL AND METHODS
There is a cross-sectional study in Caucasian postmenopausal women. They were not diagnosed with carcinoid syndrome, or bone anomalies, and received no treatment (including antiresorptives). We performed the bone formation markers: serum alkaline phosphatase (AP), serum osteocalcin (OC), and the bone resorption marker: serum CrossLaps (CL). Serum serotonin (high-pressure liquid chromatography), as well as central DXA (GE Prodigy) were assessed.
RESULTS
191 women of 57.1 years mean age were grouped according to DXA (WHO criteria). The linear regression analysis between serum serotonin and CL was not statistically significant (SS), between serotonin and OC was SS in the newly diagnosed osteoporosis group (N=40, r=0.4, p=0.03), between serotonin and AP we found SS in osteopenia group (N=88, r=0.24, p=0.03), with no changes when adjusting for age and BMI. The partial correlation between serotonin and BMD was not SS.
DISCUSSION
The study raises the question of serotonin as a bone metabolism marker seeing that the results were not consistent. The main limit of our study is that we did not analyze the possible use of antidepressants by these women. Overall, this is a pilot study in clinical practice in which few reports have been published yet, but still necessary because the use of serum serotonin in current skeletal evaluation is still unclear.
Topics: Absorptiometry, Photon; Adult; Aged; Alkaline Phosphatase; Bone Density; Cross-Sectional Studies; Female; Humans; Middle Aged; Osteocalcin; Serotonin
PubMed: 23904874
DOI: No ID Found -
European Review For Medical and... Mar 2018To observe the effects of autophagy-related gene 5 (ATG5) on the proliferation, differentiation, and apoptosis of Mc3T3-E1 osteoblast as well as the effects of ATG5 on...
OBJECTIVE
To observe the effects of autophagy-related gene 5 (ATG5) on the proliferation, differentiation, and apoptosis of Mc3T3-E1 osteoblast as well as the effects of ATG5 on apoptosis of osteoblasts under the conditions of non-oxidative stress and oxidative stress.
MATERIALS AND METHODS
ATG5 overexpressing and silencing cell lines were established in this experiment with lentiviral vector and transcription activator-like effect or nuclease (Talen) technique, respectively, using Mc3T3-E1 cells. Cell counting kit-8 (CCK-8) was used to detect the proliferation rate of osteoblasts, and flow cytometry was applied to detect the impacts of overexpressed and silenced ATG5 on the cell cycle. Alizarin red staining was used to detect the mineralization capacity of osteoblasts after 4-week osteoinduction differentiation. Quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot methods were adopted to detect the levels of gene and protein expressions of runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and collagen I (COL-I) correlated with osteoblast differentiation after 48 h of osteoinduction differentiation. The staining with Annexin V-phycoerythrin/7-amino-actinomycin D (Annexin V-PE/7AAD) and flow cytometry were performed to detect the influence of ATG5 on osteoblast apoptosis.
RESULTS
Stable ATG5 overexpressing and silencing Mc3T3-E1 cell lines were established successfully. CCK-8 test results showed that ATG5 silence inhibited cell proliferation, but the overexpression of ATG5 did not result in an obvious change in cell proliferation. Cell cycle did not change when ATG5 was overexpressed, while was stagnated in S-phase when silenced. The number of mineralized nodules of cells was reduced notably when ATG5 was silenced, while the overexpression of ATG5 did not have an impact on mineralization capacity of the cell after 4-week of osteoinduction differentiation. The test results of qRT-PCR and Western blotting suggested that ATG5 silence inhibited the gene and protein expressions of Runx2, OCN, and COL-I, while the influence of overexpressed ATG5 on the expressions of genes related to osteoblastic differentiation was not obvious after 48 h of osteoinduction differentiation. ATG5 silence made the cells easier to be damaged by hydrogen peroxide, which resulted in the rise of apoptosis rate of osteoblasts, while the overexpressed ATG5 inhibited osteoblast apoptosis after treatment with hydrogen peroxide for 12 h.
CONCLUSIONS
ATG5 silence can lead to inhibition of osteoblast proliferation and differentiation. Moreover, it makes the cells easier to be damaged by oxidative stress, and it causes an increase in apoptosis. However, the overexpression of ATG5 strengthens the anti-oxidative capacity of osteoblasts and reduces apoptosis. ATG5 may be an effective target of anti-oxidative therapy for osteoporosis, which brings a new direction for the treatment of osteoporosis.
Topics: Animals; Apoptosis; Autophagy-Related Protein 5; Cell Differentiation; Cell Proliferation; Cells, Cultured; Collagen Type I; Mice; Osteoblasts; Osteocalcin
PubMed: 29565478
DOI: 10.26355/eurrev_201803_14462 -
Cardiovascular Diabetology Jun 2015The relationship between osteocalcin and atherosclerosis remains unclear. This might be due to different degrees of confounding from factors that are associated with...
BACKGROUND
The relationship between osteocalcin and atherosclerosis remains unclear. This might be due to different degrees of confounding from factors that are associated with serum osteocalcin level, such as metabolic-related variables. This study aimed to investigate the relationship between serum osteocalcin level and carotid intima-media thickness (C-IMT) in a metabolically healthy population.
METHODS
A total of 476 subjects with normal values for weight, glucose tolerance, blood pressure, and lipids (age range, 20-75 years; 155 men, 201 premenopausal women, 120 postmenopausal women) from the Shanghai Obesity Study were recruited for this cross-sectional study. Subjects with a history of cardiovascular disease or carotid plaque were excluded. C-IMT was measured by ultrasonography. Serum osteocalcin level was assessed by an electrochemiluminescence immunoassay.
RESULTS
Median C-IMT in the entire study population was 0.55 mm with an interquartile range of 0.50-0.60 mm. C-IMT in premenopausal women was significantly lower than that in men and postmenopausal women (all P < 0.001). The median (interquartile range) of serum osteocalcin level in the entire population was 17.02 (13.31-21.47) ng/mL. Serum osteocalcin level in postmenopausal women was significantly higher than that in men and premenopausal women (all P < 0.001), while the level of serum osteocalcin in men was also significantly higher than that in premenopausal women (P < 0.001). No significant correlation was found between C-IMT and serum osteocalcin level in either men or postmenopausal women. There was a significant, inverse correlations between C-IMT and serum osteocalcin level in premenopausal women after adjustment of age, but this association was eliminated after adjustment for other confounding factors.
CONCLUSIONS
Serum osteocalcin level was not independently associated with C-IMT in a metabolically healthy Chinese population.
Topics: Adult; Aged; Carotid Arteries; Carotid Intima-Media Thickness; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Osteocalcin; Postmenopause; Premenopause; Young Adult
PubMed: 26077201
DOI: 10.1186/s12933-015-0245-9