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Current Medical Research and Opinion Apr 2020Osteocalcin is an osteoblast-derived peptide mainly found in the bone matrix but also in circulation. A recent investigation suggested that osteocalcin mediated acute...
Osteocalcin is an osteoblast-derived peptide mainly found in the bone matrix but also in circulation. A recent investigation suggested that osteocalcin mediated acute stress response (ASR) by inhibiting parasympathetic tone in mice and humans. We propose a hypothesis that osteocalcin is regulated by the skeleton movement and glucocorticoids, and inhibition of the parasympathetic tone by osteocalcin may indicate a therapeutic target in the treatment of acute myocardial infarction (AMI).
Topics: Acute Disease; Animals; Autonomic Nervous System; Bone and Bones; Heart Failure; Humans; Mice; Myocardial Infarction; Osteocalcin; Stress, Physiological
PubMed: 31990218
DOI: 10.1080/03007995.2020.1723073 -
Arteriosclerosis, Thrombosis, and... Oct 2011
Topics: Animals; Calcinosis; Cartilage; Glucose; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Osteocalcin; Vascular Diseases
PubMed: 21918209
DOI: 10.1161/ATVBAHA.111.233601 -
Nutrition Reviews Oct 1996Mice that lacked the genes for the bone protein osteocalcin were generated and were used to study the function of osteocalcin. These osteocalcin-deficient mutants had... (Review)
Review
Mice that lacked the genes for the bone protein osteocalcin were generated and were used to study the function of osteocalcin. These osteocalcin-deficient mutants had normal bones at birth but had increased bone density and thickness at 6 months. Their osteoblasts deposited more bone matrix than those of wild-type mice, though mineralization was not affected. Osteocalcin, therefore, was concluded to be a negative regulator of bone formation.
Topics: Animals; Mice; Osteocalcin
PubMed: 9063025
DOI: 10.1111/j.1753-4887.1996.tb03798.x -
The Journal of Endocrinology Apr 2015Recent developments in endocrinology, made possible by the combination of mouse genetics, integrative physiology and clinical observations have resulted in rapid and... (Review)
Review
Recent developments in endocrinology, made possible by the combination of mouse genetics, integrative physiology and clinical observations have resulted in rapid and unanticipated advances in the field of skeletal biology. Indeed, the skeleton, classically viewed as a structural scaffold necessary for mobility, and regulator of calcium-phosphorus homoeostasis and maintenance of the haematopoietic niche has now been identified as an important regulator of male fertility and whole-body glucose metabolism, in addition to the classical insulin target tissues. These seminal findings confirm bone to be a true endocrine organ. This review is intended to detail the key events commencing from the elucidation of osteocalcin (OC) in bone metabolism to identification of new and emerging candidates that may regulate energy metabolism independently of OC.
Topics: Animals; Biological Evolution; Bone and Bones; Energy Metabolism; Gene Expression Regulation; Osteocalcin
PubMed: 25655764
DOI: 10.1530/JOE-14-0584 -
Bone May 2024Osteocalcin deficient mice (OC-/-), on a mixed 129/BL6J background, were reported to show glucose intolerance, insulin insensitivity and reduced insulin secretion at 1-6...
Osteocalcin deficient mice (OC-/-), on a mixed 129/BL6J background, were reported to show glucose intolerance, insulin insensitivity and reduced insulin secretion at 1-6 mos of age. This is controversial as two studies in OC-/- mice on different backgrounds (C3H/BL6 (5-6 mos.) and C57BL/6N (5 and 9 mos.)) found no effect on glucose metabolism. To determine the role of OC in glucose metabolism we conducted glucose tolerance tests (GTT), insulin tolerances tests (ITT) and glucose stimulated insulin secretion (GSIS) on 6 and 9.5 month-old male OC-/- and OC+/+ mice on a pure C57BL/6J background and fed a normal chow diet. All results were analyzed with a two-way repeated measures ANOVA. The GTT results showed no effect on males at 6 months of age but glucose intolerance was significantly increased (p < 0.05) in male OC-/- mice at 9.5 months of age. The ITT results indicated significantly increased insulin resistance in male OC-/- mice. Glucose stimulated insulin secretion (GSIS) showed insulin significantly (p < 0.05) reduced in OC-/- at several time points. Mouse Osteocalcin injected into OC-/- mice decreased the glucose level. Our results confirm the role of OC in glucose metabolism and insulin sensitivity and demonstrate a role in insulin secretion in older male mice on a C57BL/6J background. Differences in background, age, or experimental procedures could explain controversial results. A delayed onset of the effect of OC on glucose metabolism at 9.5 months in male C57BL/6J mice highlights the importance of background on phenotype. Consideration of genetic background and age may be beneficial for human studies on osteocalcin and glucose homeostasis and may be relevant to the elderly where osteocalcin is reduced.
Topics: Animals; Mice; Blood Glucose; Glucose; Glucose Intolerance; Insulin; Insulin Resistance; Mice, Inbred C3H; Mice, Inbred C57BL; Osteocalcin; Aging
PubMed: 38378083
DOI: 10.1016/j.bone.2024.117048 -
Minerva Endocrinologica 1989The field of metabolic bone diseases has recently received useful information from the examination of the role of new collagenous and non-collagenous bone proteins, such... (Review)
Review
The field of metabolic bone diseases has recently received useful information from the examination of the role of new collagenous and non-collagenous bone proteins, such as osteocalcin (also called bone Gla-protein) and osteonectin. It appears that at present, serum osteocalcin is the one bone protein that has the most promise for assisting in the diagnosis and management of high turnover metabolic bone disease states. Since endocrine diseases are frequently associated with altered bone turnover due to a disequilibrium between formation and bone resorption, we examine the role of osteocalcin, a specific marker of osteoblastic activity, in these clinical conditions.
Topics: Bone Diseases, Metabolic; Humans; Osteocalcin
PubMed: 2695817
DOI: No ID Found -
Reproductive Biology Dec 2021Evidence for the role of osteocalcin in glucose metabolism is increasing. The aim of this study was to examine the associations between osteocalcin and gestational...
Evidence for the role of osteocalcin in glucose metabolism is increasing. The aim of this study was to examine the associations between osteocalcin and gestational diabetes mellitus. Thirteen discovery study subjects and 76 reduplication study subjects were recruited from the Maternal and Child Health Hospital Guangxi Zhuang Autonomous Region from May 2018 to August 2018. Total osteocalcin and biochemical indices of maternal serum and umbilical vein serum were analyzed. Placental tissue samples were used for transcriptome sequencing. For the discovery study subjects, the total osteocalcin concentration in umbilical vein serum was significantly higher than that in maternal serum and umbilical artery serum (55.32 ng/mL ± 17.37 vs. 12.06 ng/mL ± 5.42 [P < 0.001] vs. 38.31 ng/mL ± 11.52 [P < 0.01]), suggesting that trophoblasts may synthesize osteocalcin. In a reduplication subject study, the gestational diabetes mellitus group had lower umbilical vein serum total osteocalcin (51.46 ng/mL ± 24.29 vs. 67.00 ng/mL ± 25.33, P = 0.008), lower adiponectin (1099.72 μg/L ± 102.65 vs. 1235.85 μg/L ± 94.63, P < 0.001). Spearman's correlation analysis showed that umbilical vein serum total osteocalcin levels were closely correlated with leptin (r = -0.456, P = 0.007). A coexpression model of the placental RNA sequence was constructed. Two modules were correlated with osteocalcin, and the Gene ontology pathways of these modules were rich in glucose and lipid metabolism. In conclusion, the placenta may synthesize osteocalcin by itself, and a lower osteocalcin level in umbilical vein serum is associated with gestational diabetes mellitus.
Topics: Adult; Blood Glucose; Cell Proliferation; Diabetes, Gestational; Female; Humans; Osteocalcin; Placenta; Pregnancy; RNA, Messenger; Trophoblasts
PubMed: 34626941
DOI: 10.1016/j.repbio.2021.100566 -
The Journal of Clinical Investigation Feb 2022Osteocalcin is a hormone produced in bones by osteoblasts during bone formation. Numerous studies have demonstrated that adrenal gland-derived glucocorticoids inhibit...
Osteocalcin is a hormone produced in bones by osteoblasts during bone formation. Numerous studies have demonstrated that adrenal gland-derived glucocorticoids inhibit osteocalcin production, which can ultimately cause deleterious bones loss. This loss establishes a unidirectional endocrine relationship between the adrenal glands and bone, however, whether osteocalcin reciprocally regulates glucocorticoid secretion remains unclear. In this issue of the JCI, Yadav and colleagues address how bone-derived osteocalcin influences adrenal organogenesis and function. Using a large variety of animal models, the authors established that embryonic osteocalcin signaling, specifically through the GPR158 receptor, regulates postnatal adrenal steroid concentrations throughout life. This work has translational potential, and we await future investigations that determine whether modulating osteocalcin levels could promote endogenous adrenocortical function in adrenocortical hypoplasia and glucocorticoid deficiency.
Topics: Animals; Bone and Bones; Glucocorticoids; Osteoblasts; Osteocalcin; Osteogenesis
PubMed: 35166237
DOI: 10.1172/JCI157200 -
Osteoporosis International : a Journal... Aug 2017Undercarboxylated osteocalcin (ucOC) may play a role in glucose homeostasis and cardiometabolic health. This review examines the epidemiological and interventional... (Review)
Review
Undercarboxylated osteocalcin (ucOC) may play a role in glucose homeostasis and cardiometabolic health. This review examines the epidemiological and interventional evidence associating osteocalcin (OC) and ucOC with metabolic risk and cardiovascular disease. The complexity in assessing such correlations, due to the observational nature of human studies, is discussed. Several studies have reported that higher levels of ucOC and OC are correlated with lower fat mass and HbA1c. In addition, improved measures of glycaemic control via pharmacological and non-pharmacological (e.g. exercise or diet) interventions are often associated with increased circulating levels of OC and/or ucOC. There is also a relationship between lower circulating OC and ucOC and increased measures of vascular calcification and cardiovascular disease. However, not all studies have reported such relationship, some with contradictory findings. Equivocal findings may arise because of the observational nature of the studies and the inability to directly assess the relationship between OC and ucOC on glycaemic control and cardiovascular health in humans. Studying OC and ucOC in humans is further complicated due to numerous confounding factors such as sex differences, menopausal status, vitamin K status, physical activity level, body mass index, insulin sensitivity (normal/insulin resistance/T2DM), tissue-specific effects and renal function among others. Current observational and indirect interventional evidence appears to support a relationship between ucOC with metabolic and cardiovascular disease. There is also emerging evidence to suggest a direct role of ucOC in human metabolism. Further mechanistic studies are required to (a) clarify causality, (b) explore mechanisms involved and
Topics: Blood Glucose; Cardiovascular Diseases; Exercise; Humans; Hypoglycemic Agents; Insulin Resistance; Life Style; Metabolic Syndrome; Osteocalcin; Vitamin K
PubMed: 28289780
DOI: 10.1007/s00198-017-3994-3 -
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