-
Medicina (Kaunas, Lithuania) Aug 2020Osteocalcin is the most abundant noncollagenous protein in bone matrix, which is considered a marker of bone formation. Previous studies indicate that circulating...
BACKGROUND AND OBJECTIVES
Osteocalcin is the most abundant noncollagenous protein in bone matrix, which is considered a marker of bone formation. Previous studies indicate that circulating osteocalcin can be expressed by osteoblasts and even by osteoblast-like cells in vessel walls, and it is often associated with arterial stiffness. Our study aims to examine the potential association between osteocalcin levels and endothelial function among kidney transplant (KT) recipients.
MATERIALS AND METHODS
Fasting blood samples were obtained from 68 KT recipients. To measure the endothelial function and vascular reactivity index (VRI), a digital thermal monitoring test (VENDYS) was used. A commercial enzyme-linked immunosorbent assay kit was also utilized to measure serum total osteocalcin levels. In this study, a VRI of less than 1.0 indicated poor vascular reactivity; a VRI of 1.0-2.0 indicated intermediate vascular reactivity; and a VRI of 2.0 or higher indicated good vascular reactivity.
RESULTS
Our findings show that 8 KT recipients (11.8%) had poor vascular reactivity (VRI < 1.0), 26 (38.2%) had intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 34 (50%) had good vascular reactivity. Increased serum osteocalcin levels ( < 0.001) were found to be associated with poor vascular reactivity. Advanced age ( = -0.361, = 0.002), serum alkaline phosphate level ( = -0.254, = 0.037), and log-transformed osteocalcin levels ( = - 0.432, < 0.001) were identified to be negatively correlated with VRI in KT recipients. Multivariable forward stepwise linear regression analysis revealed that the serum level of osteocalcin (β = -0.391, adjusted R change = 0.174; < 0.001) and advanced age (β = -0.308, adjusted R change = 0.084; = 0.005) were significantly and independently associated with VRI in KT recipients.
CONCLUSIONS
Higher serum osteocalcin level was associated with lower VRI and poorer endothelial dysfunction among KT recipients.
Topics: Adult; Body Mass Index; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Osteocalcin; Pulse Wave Analysis; Taiwan; Vascular Stiffness
PubMed: 32784817
DOI: 10.3390/medicina56080400 -
Journal of Veterinary Diagnostic... Nov 2020Traumatic injury, including bone fracture, is, to date, one of the leading causes of koala mortality in the South East Queensland region of Australia. Further, the...
Traumatic injury, including bone fracture, is, to date, one of the leading causes of koala mortality in the South East Queensland region of Australia. Further, the specialist diet of koalas, which is restricted to certain spp., may impact their normal bone physiology. Considering the dramatic koala population decline and high incidence of trauma, a greater understanding of koala bone physiology may support conservation. We retrieved from GenBank the protein sequences of parathyroid hormone (PTH), osteocalcin (OCN), and tissue-nonspecific alkaline phosphatase (TNALP) in human, dog, cattle, horse, koala, and gray short-tailed opossum. After homology was determined, plasma samples from 13 koalas were analyzed with human PTH, OCN, and bone-specific ALP (BALP) assay kits. Although koala PTH exhibited relatively low sequence homology with placental mammals, high sequence homology between humans and koalas was observed for both OCN and TNALP, and successful cross-reactivity was achieved using human enzyme immunoassay kits for detection of OCN and BALP biomarkers in koala plasma. However, we identified no correlation between OCN and BALP concentrations of healthy and trauma-affected koalas ( = 0.66 and = 0.79, respectively). Further analysis of OCN and BALP in healthy and diseased koalas will allow a better understanding of bone physiology in this unique marsupial.
Topics: Amino Acid Sequence; Animals; Biological Assay; Female; Immunoenzyme Techniques; Phascolarctidae; Pregnancy; Queensland
PubMed: 32917121
DOI: 10.1177/1040638720957031 -
Cell Metabolism Nov 2019We hypothesized that bone evolved, in part, to enhance the ability of bony vertebrates to escape danger in the wild. In support of this notion, we show here that a...
We hypothesized that bone evolved, in part, to enhance the ability of bony vertebrates to escape danger in the wild. In support of this notion, we show here that a bone-derived signal is necessary to develop an acute stress response (ASR). Indeed, exposure to various types of stressors in mice, rats (rodents), and humans leads to a rapid and selective surge of circulating bioactive osteocalcin because stressors favor the uptake by osteoblasts of glutamate, which prevents inactivation of osteocalcin prior to its secretion. Osteocalcin permits manifestations of the ASR to unfold by signaling in post-synaptic parasympathetic neurons to inhibit their activity, thereby leaving the sympathetic tone unopposed. Like wild-type animals, adrenalectomized rodents and adrenal-insufficient patients can develop an ASR, and genetic studies suggest that this is due to their high circulating osteocalcin levels. We propose that osteocalcin defines a bony-vertebrate-specific endocrine mediation of the ASR.
Topics: Adrenal Insufficiency; Adrenalectomy; Adult; Animals; Bone and Bones; Cells, Cultured; Female; Glutamic Acid; Healthy Volunteers; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Neurons; Osteoblasts; Osteocalcin; Parasympathetic Nervous System; Rats; Rats, Sprague-Dawley; Stress, Physiological
PubMed: 31523009
DOI: 10.1016/j.cmet.2019.08.012 -
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 -
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 -
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 -
Biochemical and Biophysical Research... Jul 2010Osteocalcin was recently identified as an osteoblast-secreted hormone regulating insulin secretion and sensitivity. In mice and humans, osteocalcin can be present in the...
Osteocalcin was recently identified as an osteoblast-secreted hormone regulating insulin secretion and sensitivity. In mice and humans, osteocalcin can be present in the serum in carboxylated or undercarboxylated forms and it has been shown that it is the undercarboxylated form of osteocalcin which acts as a hormone. The study of osteocalcin different circulating forms in mouse serum, however, has been hampered by the absence of quantitative methodology. Here we described a triple enzyme-linked immunosorbent assay (ELISA) system for quantification of mouse total, carboxylated and uncarboxylated osteocalcin. That carboxylation of osteocalcin was decreased in mouse osteoblasts cultures treated with warfarin, an inhibitor of carboxylation validated this assay. This ELISA could also detect elevated levels of undercarboxylated osteocalcin in the serum of mice treated with warfarin and in the serum of Esp -/- mice, a mouse model known to have more undercarboxylated, i.e., active osteocalcin. These results show that this new ELISA system is a reliable method to assess carboxylation status of osteocalcin in cell culture supernatants as well as in mouse serum. Its use should facilitate the analysis of culture system or mouse model in which the hormonal activity of osteocalcin needs to be evaluated.
Topics: Animals; Antibodies; Cells, Cultured; Culture Media; Enzyme-Linked Immunosorbent Assay; Mice; Mice, Mutant Strains; Osteoblasts; Osteocalcin; Warfarin
PubMed: 20570657
DOI: 10.1016/j.bbrc.2010.06.008 -
Blood Jan 2021γ-Glutamyl carboxylase (GGCX) is an integral membrane protein that catalyzes posttranslational carboxylation of a number of vitamin K-dependent (VKD) proteins involved...
γ-Glutamyl carboxylase (GGCX) is an integral membrane protein that catalyzes posttranslational carboxylation of a number of vitamin K-dependent (VKD) proteins involved in a wide variety of physiologic processes, including blood coagulation, vascular calcification, and bone metabolism. Naturally occurring GGCX mutations are associated with multiple distinct clinical phenotypes. However, the genotype-phenotype correlation of GGCX remains elusive. Here, we systematically examined the effect of all naturally occurring GGCX mutations on the carboxylation of 3 structure-function distinct VKD proteins in a cellular environment. GGCX mutations were transiently introduced into GGCX-deficient human embryonic kidney 293 cells stably expressing chimeric coagulation factor, matrix Gla protein (MGP), or osteocalcin as VKD reporter proteins, and then the carboxylation efficiency of these reporter proteins was evaluated. Our results show that GGCX mutations differentially affect the carboxylation of these reporter proteins and the efficiency of using vitamin K as a cofactor. Carboxylation of these reporter proteins by a C-terminal truncation mutation (R704X) implies that GGCX's C terminus plays a critical role in the binding of osteocalcin but not in the binding of coagulation factors and MGP. This has been confirmed by probing the protein-protein interaction between GGCX and its protein substrates in live cells using bimolecular fluorescence complementation and chemical cross-linking assays. Additionally, using a minigene splicing assay, we demonstrated that several GGCX missense mutations affect GGCX's pre-messenger RNA splicing rather than altering the corresponding amino acid residues. Results from this study interpreted the correlation of GGCX's genotype and its clinical phenotypes and clarified why vitamin K administration rectified bleeding disorders but not nonbleeding disorders.
Topics: Amino Acid Sequence; Base Sequence; Calcium-Binding Proteins; Carbon-Carbon Ligases; Carboxy-Lyases; Extracellular Matrix Proteins; Genes, Reporter; Genetic Association Studies; Genetic Pleiotropy; HEK293 Cells; Hemorrhagic Disorders; Humans; Mutation; Mutation, Missense; Osteocalcin; Protein C; Protein Domains; Protein Interaction Mapping; Protein Isoforms; Protein Processing, Post-Translational; RNA Precursors; RNA Splicing; Recombinant Fusion Proteins; Structure-Activity Relationship; Vitamin K; Matrix Gla Protein
PubMed: 33507293
DOI: 10.1182/blood.2020006329 -
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 -
Biological Research Nov 2015Tridax procumbens flavonoids (TPFs) are well known for their medicinal properties among local natives. Besides traditionally used for dropsy, anemia, arthritis, gout,...
BACKGROUND
Tridax procumbens flavonoids (TPFs) are well known for their medicinal properties among local natives. Besides traditionally used for dropsy, anemia, arthritis, gout, asthma, ulcer, piles, and urinary problems, it is also used in treating gastric problems, body pain, and rheumatic pains of joints. TPFs have been reported to increase osteogenic functioning in mesenchymal stem cells. Our previous study showed that TPFs were significantly suppressed the RANKL-induced differentiation of osteoclasts and bone resorption. However, the effects of TPFs to promote osteoblasts differentiation and bone formation remain unclear. TPFs were isolated from Tridax procumbens and investigated for their effects on osteoblasts differentiation and bone formation by using primary mouse calvarial osteoblasts.
RESULTS
TPFs promoted osteoblast differentiation in a dose-dependent manner demonstrated by up-regulation of alkaline phosphatase and osteocalcin. TPFs also upregulated osteoblast differentiation related genes, including osteocalcin, osterix, and Runx2 in primary osteoblasts. TPFs treated primary osteoblast cells showed significant upregulation of bone morphogenetic proteins (BMPs) including Bmp-2, Bmp-4, and Bmp-7. Addition of noggin, a BMP specific-antagonist, inhibited TPFs induced upregulation of the osteocalcin, osterix, and Runx2.
CONCLUSION
Our findings point towards the induction of osteoblast differentiation by TPFs and suggested that TPFs could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.
Topics: Alkaline Phosphatase; Animals; Asteraceae; Bone Morphogenetic Proteins; Calcification, Physiologic; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Flavonoids; Medicine, Traditional; Mice, Inbred C57BL; Osteoblasts; Osteocalcin; Osteogenesis; Primary Cell Culture; Reverse Transcriptase Polymerase Chain Reaction; Skull; Sp7 Transcription Factor; Transcription Factors; Up-Regulation
PubMed: 26581452
DOI: 10.1186/s40659-015-0056-1