Fact-checked by Grok 2 weeks ago

Osteocalcin

Osteocalcin, also known as bone Gla protein (BGP), is a small vitamin K-dependent protein encoded by the BGLAP gene on chromosome 1q22 and synthesized primarily by osteoblasts, making it the most abundant non-collagenous protein in bone tissue.^[1]^[2] It consists of 46–50 amino acids with a molecular weight of approximately 5.6 kDa and features a Gla domain containing three gamma-carboxyglutamic acid (Gla) residues that enable calcium binding.^[1] In its carboxylated form, osteocalcin primarily functions in bone mineralization by regulating hydroxyapatite crystal size, shape, and maturation within the extracellular matrix.^[3] The undercarboxylated form (ucOC), generated during bone resorption under low pH conditions, circulates systemically and exerts endocrine effects.^[3] Discovered in the late 1970s through isolation from bovine and human bone, osteocalcin was initially identified for its role in bone formation but later recognized for broader physiological impacts.^[1] Its synthesis is tightly regulated by vitamin K, which facilitates post-translational gamma-carboxylation of glutamic acid residues, and by insulin signaling in osteoblasts that promotes its production and activation via osteoclast-mediated bone resorption.^[3] Osteocalcin is also expressed at lower levels in odontoblasts and hypertrophic chondrocytes, contributing to dentin and cartilage mineralization, respectively.^[4] Clinically, serum levels of osteocalcin serve as a biomarker for bone turnover, with elevated concentrations indicating increased osteoblast activity in conditions like osteoporosis or Paget's disease, and reduced levels linked to metabolic disorders.^[5] Beyond bone, osteocalcin has been proposed to function as an osteoblast-derived hormone that influences multiple systems, with roles well-documented in animal models but under debate in humans.^[6] In glucose metabolism, ucOC enhances beta-cell proliferation, insulin gene expression, and insulin sensitivity in peripheral tissues via the GPRC6A receptor, thereby improving glucose tolerance; studies in osteocalcin-null mice demonstrate hyperglycemia and glucose intolerance, underscoring this role.^[3] It also regulates energy homeostasis by reducing visceral fat mass and promoting adaptations to exercise.^[3] In reproduction, ucOC stimulates testosterone biosynthesis in Leydig cells via GPRC6A, supporting male fertility, as evidenced by reduced testosterone and impaired breeding in knockout models.^[3] Additionally, it crosses the blood-brain barrier to modulate neuronal development, cognition, and anxiety-like behaviors via the GPR158 receptor.^[7] These multifaceted roles highlight osteocalcin's integration of skeletal and metabolic physiology.^[8]

Molecular Structure and Genetics

Protein Structure

Osteocalcin is a small, non-collagenous protein consisting of 49 amino acids in humans, with a molecular weight of approximately 5.9 kDa.^[9] It represents one of the most abundant non-collagenous proteins in the bone matrix, comprising up to 15-20% of this fraction.^[10] This protein's non-collagenous nature distinguishes it from the primary structural components of bone extracellular matrix, such as type I collagen, and underscores its specialized role in mineralization processes. The primary amino acid sequence of mature human osteocalcin begins with Tyr-Leu-Tyr-Gln-Trp-Leu-Gly-Ala-Pro-Val-Pro-Tyr-Pro-Asp-Pro-Leu and continues through to Gly-Pro-Val at the C-terminus, forming a single polypeptide chain stabilized by a disulfide bond between cysteine residues at positions 23 and 29. Within this sequence, three glutamic acid residues at positions 17, 21, and 24 are sites for post-translational gamma-carboxylation to gamma-carboxyglutamic acid (Gla), which confers calcium-binding capability essential for the protein's interaction with hydroxyapatite.^[11] These Gla residues are conserved across vertebrate homologs, though the overall sequence length varies; for instance, rodent osteocalcin is shorter, with 46 amino acids in mice due to deletions in the N-terminal region.^[1] In its calcium-bound form, osteocalcin adopts a compact three-dimensional conformation characterized by two anti-parallel alpha-helical segments (residues 16-25 and 30-41) connected by a beta-turn (residues 26-29), along with additional beta-sheet elements and irregular turns.^[12] This arrangement forms a calcium-binding motif akin to those in other vitamin K-dependent Gla proteins, where the Gla residues coordinate calcium ions to facilitate binding to mineral surfaces, though the structure remains largely disordered in the absence of calcium.^[11] The overall fold enables high-affinity interactions with bone mineral while maintaining solubility in the extracellular environment.^[13]

Gene and Expression

Osteocalcin is encoded by the BGLAP gene (Bone Gamma-Carboxyglutamate Protein), which is located on the long arm of human chromosome 1 at position 1q22 (genomic coordinates GRCh38: 1:156,242,184-156,243,317).^[2] This gene spans approximately 1.1 kb of genomic DNA and consists of four exons separated by three introns, with the majority of the coding sequence contained within the final three exons.^[14] The promoter region upstream of the first exon includes osteoblast-specific regulatory elements, notably multiple binding sites for the transcription factor Runx2, which is essential for directing tissue-specific transcription.^[15] The BGLAP gene was first identified in 1975 as part of investigations into vitamin K-dependent, calcium-binding proteins in bone matrix, independently reported by Hauschka et al. and Price et al.. Orthologs are conserved across mammals, with mice possessing two closely related genes, Bglap (also known as Bglap1) and Bglap2, which together fulfill similar functions to the single human BGLAP.^[16] Expression of BGLAP is highly tissue-specific, predominantly confined to bone with minimal detectable levels in other tissues such as kidney, lung, or brain, reflecting its role in skeletal biology. Within bone, transcription occurs primarily in mature osteoblasts and is markedly upregulated during the late stages of osteoblast differentiation, coinciding with matrix mineralization.^[17] Regulation of BGLAP transcription is tightly controlled to align with osteoblast maturation. Bone morphogenetic protein (BMP) signaling, particularly via BMP-2, induces BGLAP expression by activating downstream pathways that enhance osteoblast-specific gene programs.^[18] Similarly, 1,25-dihydroxyvitamin D3 (the active form of vitamin D) stimulates transcription through direct interaction with vitamin D response elements in the promoter, often in cooperation with Runx2.^[19] In contrast, inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) repress BGLAP expression at the transcriptional level, potentially via disruption of vitamin D receptor binding or induction of inhibitory factors, thereby linking bone remodeling to systemic inflammation.^[20]

Biosynthesis and Post-Translational Modification

Synthesis in Osteoblasts

Osteocalcin is synthesized primarily by osteoblasts, the bone-forming cells derived from mesenchymal stem cells, specifically during the late stages of their differentiation when bone mineralization is initiated. This production is tightly regulated and serves as a hallmark of mature osteoblast function, with osteocalcin mRNA expression and protein output increasing as osteoblasts transition from proliferation to matrix deposition phases.^[21]^[1] The biosynthesis process commences with the translation of osteocalcin mRNA on ribosomes bound to the rough endoplasmic reticulum within osteoblasts. The resulting pre-pro-osteocalcin polypeptide, approximately 98 amino acids in length, is co-translationally translocated into the endoplasmic reticulum lumen, where it undergoes initial folding assisted by chaperones. A signal peptide comprising the first 23 amino acids is then cleaved by signal peptidase, yielding pro-osteocalcin and enabling further processing for secretion. This ribosomal translation and early folding occur efficiently, reflecting osteocalcin's role as a major secretory product in these cells.^[22]^[21]^[1] Following processing in the endoplasmic reticulum, pro-osteocalcin traffics through the Golgi apparatus via the classical secretory pathway, involving vesicular transport, and is released into the extracellular space. A portion is directed to the bone extracellular matrix, while some enters the circulation. Osteocalcin constitutes about 10-20% of the non-collagenous proteins produced by osteoblasts, underscoring its abundance in the secretory output during peak synthesis, which occurs in fully differentiated osteoblasts immediately preceding active mineralization.^[21]^[23] Upon secretion into the bone matrix, osteocalcin rapidly integrates by binding to hydroxyapatite crystals, the primary mineral component of bone, through its calcium-coordinating motifs, thereby contributing to the structural organization of the mineralized tissue. This binding facilitates its incorporation without disrupting the ongoing mineralization process.^[21]^[1]

Carboxylation and Forms

Osteocalcin undergoes a critical post-translational modification known as γ-carboxylation, in which specific glutamic acid residues are converted to γ-carboxyglutamic acid (Gla) residues by the enzyme γ-glutamyl carboxylase (GGCX).^[24] This process requires reduced vitamin K (KH₂) as a cofactor, along with carbon dioxide and oxygen, and occurs in the endoplasmic reticulum of osteoblasts after initial protein synthesis.^[25] The modification was first identified in the 1970s when two independent research groups isolated a vitamin K-dependent protein from bovine bone containing three Gla residues, initially termed bone Gla protein. The extent of carboxylation determines the primary isoforms of osteocalcin: fully carboxylated osteocalcin (cOC), which contains three Gla residues, and undercarboxylated osteocalcin (ucOC), which has 0 to 2 Gla residues due to incomplete modification.^[26] In humans, cOC predominates in the bone matrix, comprising 90-95% of total osteocalcin, owing to its enhanced affinity for hydroxyapatite that facilitates incorporation into mineralized tissue.^[25] In contrast, ucOC constitutes up to 30% of circulating osteocalcin in healthy individuals, reflecting variable carboxylation efficiency influenced by vitamin K availability.^[27] Carboxylation efficiency is highly dependent on vitamin K status; deficiency impairs GGCX activity, leading to an elevated ucOC ratio in both bone and serum.^[24] The Gla residues in cOC confer high-affinity calcium binding, with a dissociation constant (K_d) of approximately 10^{-6} M, enabling strong interactions with calcium ions and hydroxyapatite, whereas ucOC exhibits substantially lower affinity.^[25] This biochemical distinction underlies the differential distribution and potential roles of the isoforms, though full functional implications extend beyond structural properties.

Physiological Functions

Role in Bone Mineralization

Carboxylated osteocalcin (cOC), the γ-carboxyglutamic acid-containing form of the protein, plays a central role in bone mineralization by binding calcium ions and hydroxyapatite crystals within the extracellular matrix of bone. This high-affinity interaction enables cOC to regulate the growth, size, and alignment of hydroxyapatite crystallites, thereby controlling mineral deposition and preventing excessive or disordered crystal formation that could compromise bone quality. By facilitating the parallel orientation of apatite crystals along collagen fibrils, cOC ensures the biomechanical strength and ordered structure of the mineralized matrix.^[6] As a key non-collagenous protein, osteocalcin functions as a scaffold in the bone extracellular matrix, modulating the assembly and organization of collagen fibrils to support mineral nucleation and integration during osteoblast-mediated bone formation. This scaffolding role helps maintain the hierarchical architecture of bone tissue, where mineral crystals are precisely embedded within the organic collagen framework.^[6] Evidence from osteocalcin knockout mouse models highlights its potential inhibitory function in mineralization; early studies show these animals exhibit increased bone formation rates, trabecular volume, and overall bone density compared to wild-type controls, indicating that endogenous osteocalcin exerts negative feedback to fine-tune mineral accrual and prevent hypermineralization, though more recent strain-specific models demonstrate variable effects. During the bone remodeling cycle, osteocalcin is released from the matrix by osteoclasts through proteolytic fragmentation and decarboxylation in the acidic resorption environment, allowing recirculation and replenishment for subsequent formation phases. Vitamin K status critically impacts this process, as the vitamin is essential for the post-translational γ-carboxylation of osteocalcin; deficiencies lead to undercarboxylated forms with reduced matrix-binding affinity, thereby impairing bone mineral quality and strength.^[28]^[29]^[30]^[24]

Endocrine Functions

Uncarboxylated osteocalcin (ucOC), a circulating form derived from the decarboxylation of osteoblast-secreted carboxylated osteocalcin during bone resorption and lacking gamma-carboxylation on specific glutamate residues, functions as an osteokine with endocrine effects on distant tissues.^[31] This hormonal role was first identified in 2007 by researchers in the Karsenty laboratory, who demonstrated through genetic mouse models that ucOC regulates systemic energy metabolism.^[31] ucOC exerts these effects primarily by binding to the G protein-coupled receptor GPRC6A, which is expressed in various target cells, thereby influencing multiple physiological pathways. While these effects are causally demonstrated in mouse models, human evidence is largely associative, with ucOC levels correlating to metabolic outcomes but intervention trials showing mixed results.^[32]^[33] In metabolic regulation, ucOC promotes insulin secretion and beta-cell proliferation in the pancreas via GPRC6A activation, enhancing glucose homeostasis.^[33] It also stimulates adiponectin expression in adipocytes, an insulin-sensitizing hormone that further supports glucose handling and reduces fat accumulation.^[31] Mouse studies lacking osteocalcin exhibit glucose intolerance, reduced beta-cell mass, lower insulin levels, and diminished energy expenditure, underscoring ucOC's necessity for metabolic balance.^[31] In humans, circulating ucOC levels inversely correlate with markers of metabolic syndrome, including body mass index, fasting glucose, insulin resistance (measured by HOMA-IR), and triglyceride levels, while positively associating with adiponectin.^[34] Regarding reproduction, ucOC enhances male fertility by binding GPRC6A on Leydig cells to boost testosterone biosynthesis from cholesterol precursors.^[35] This signaling also supports spermatogenesis, as evidenced by reduced testis size, lower testosterone, and impaired sperm production in osteocalcin-deficient male mice, which show decreased fertility rates.^[35] ucOC operates through a pancreas-bone-testis axis, where insulin further modulates osteocalcin activity to fine-tune these reproductive processes.^[36] Emerging research highlights ucOC's roles beyond metabolism and reproduction. In the brain, ucOC crosses the blood-brain barrier and binds GPR158, a G protein-coupled receptor in hippocampal neurons, to regulate cognition and anxiety; osteocalcin-deficient mice display memory deficits and heightened anxiety-like behaviors, which are rescued by ucOC administration that restores hippocampal synaptic plasticity and brain-derived neurotrophic factor expression.^[7] In skeletal muscle, ucOC signaling via GPRC6A in myofibers is essential for exercise adaptation, promoting glucose and fatty acid uptake to increase energy expenditure and endurance capacity by up to 30% in mouse models.^[37] Bone-derived ucOC circulates in plasma in an unbound state, facilitating rapid diffusion to target tissues, with a half-life of approximately 1 hour that supports its acute regulatory functions.^[38]

Clinical Significance

Biomarker for Bone Turnover

Serum total osteocalcin (tOC) serves as a key biomarker for bone formation, primarily reflecting the activity of osteoblasts in synthesizing and releasing this protein into the bloodstream.^[39] Levels of tOC correlate with the rate of bone matrix formation and are widely used to assess overall bone turnover dynamics.^[40] A common assay for measuring tOC is the N-terminal mid-fragment (N-MID) immunoassay, which targets the mid-region of the osteocalcin molecule and provides reliable quantification in clinical settings.^[41] In adults, normal serum tOC levels typically range from 10 to 50 ng/mL, though reference intervals vary by age, sex, and assay method, with higher values observed in postmenopausal women and lower levels in older men.^[42] Elevated tOC concentrations are characteristic of high bone turnover states, such as during childhood growth or in conditions like Paget's disease, where osteoblast activity is markedly increased.^[43] These variations underscore the importance of age- and sex-specific reference ranges for accurate interpretation.^[44] Uncarboxylated osteocalcin (ucOC) functions as a specific marker of vitamin K status and bone turnover, with higher levels indicating impaired γ-carboxylation due to vitamin K deficiency.^[45] The ratio of ucOC to carboxylated osteocalcin (cOC), often expressed as the percentage of ucOC (%ucOC), provides a direct measure of carboxylation efficiency and is inversely associated with bone health outcomes.^[46] Assay methods for osteocalcin primarily involve immunoassays, including enzyme-linked immunosorbent assay (ELISA) for both tOC and ucOC detection, as well as electrochemiluminescence immunoassays that offer high sensitivity and automation for routine clinical use.^[47] Challenges in measurement include circadian rhythm variations, with peak levels occurring nocturnally, and renal clearance, which can elevate circulating concentrations in patients with impaired kidney function.^[48] Standardized sample collection, such as morning fasting blood draws, is recommended to minimize these influences.^[39] In clinical practice, osteocalcin measurements are particularly useful for monitoring the response to antiresorptive therapies, such as bisphosphonates, where a significant decline in tOC levels (often >30% within 3-6 months) indicates effective suppression of bone turnover and treatment adherence.^[49] This application enhances the ability to adjust therapeutic strategies promptly, improving outcomes in osteoporosis management.^[50]

Associations with Diseases

Osteocalcin, particularly its undercarboxylated form (ucOC), has been inversely associated with type 2 diabetes (T2D), insulin resistance, and metabolic syndrome in several human studies, where lower circulating ucOC levels correlate with higher fasting glucose, impaired insulin sensitivity, and increased adiposity markers.^[51]^[52] This suggests ucOC may act as a protective hormone in glucose homeostasis, potentially serving as a therapeutic target to improve insulin secretion and sensitivity in these conditions.^[53] However, discrepancies exist, as some cohort studies report no significant correlation between ucOC and insulin resistance in T2D patients, highlighting challenges in translating findings to human physiology.^[54] In bone-related disorders, total osteocalcin (tOC) levels are often elevated, reflecting increased bone turnover. For instance, serum tOC is raised in osteoporosis due to enhanced osteoblast activity and bone remodeling, as well as in primary hyperparathyroidism from parathyroid hormone-driven bone resorption and formation.^[55]^[56] Similarly, elevated tOC occurs in bone metastases, where tumor-induced osteolysis accelerates osteoblast response.^[55] Conversely, in renal osteodystrophy—particularly the low-turnover subtype like adynamic bone disease—tOC levels are decreased, attributed to suppressed osteoblast function and impaired mineralization in chronic kidney disease.^[57] Recent studies from 2024 have linked low total osteocalcin (tOC) to cognitive decline and Alzheimer's disease (AD), with Mendelian randomization analyses indicating a causal protective effect of higher circulating osteocalcin against AD risk, potentially through reduced neuroinflammation and amyloid burden.^[58] In male reproductive health, ucOC deficiency is associated with infertility, as it promotes testosterone biosynthesis in Leydig cells; elevated ucOC levels have been observed in some forms of hypogonadism, potentially as a compensatory response, though disruptions contribute to impaired spermatogenesis and fertility in animal models.^[59]^[60] Vitamin K deficiency exacerbates fracture risk by reducing carboxylated osteocalcin (cOC), which impairs bone mineralization and matrix binding, as evidenced by higher undercarboxylation ratios in fracture-prone individuals.^[61] In neuropsychiatric contexts, the GPR158-osteocalcin axis modulates anxiety disorders; osteocalcin signaling via GPR158 in hippocampal and prefrontal neurons suppresses anxiety-like behaviors and supports cognitive resilience, with disruptions linked to stress-induced psychopathology.^[62] These associations underscore osteocalcin's endocrine roles in brain health, though mouse models show stronger metabolic effects than human data, where osteocalcin's hormonal influence on energy metabolism remains debated due to species-specific differences in expression and receptor function.^[6]

References

[1]
New Insights into the Biology of Osteocalcin - PMC - PubMed Central
Osteocalcin is among the most abundant proteins in bone and is produced exclusively by osteoblasts. Initially believed to be an inhibitor of bone ...
[2]
BGLAP bone gamma-carboxyglutamate protein [ (human)] - NCBI
Aug 19, 2025 · Osteocalcin plays an essential role for the maturation of mineral species and modulates osteogenic differentiation of mesenchymal stromal cells ...
[3]
An overview of the metabolic functions of osteocalcin - PMC
Osteocalcin is an osteoblast-specific gene encoding a secreted protein that was identified in the late 70's but whose functions in the pre-model organism ...
[4]
A four-season molecule: osteocalcin. Updates in its physiological roles
Osteocalcin (OC) is the main non-collagenous hydroxyapatite-binding protein synthesized by osteoblasts, odontoblasts, and hypertrophic chondrocytes.
[5]
Osteocalcin: Beyond Bones - PMC - PubMed Central - NIH
Osteocalcin, the most abundant non-collagenous protein in bone tissue, is routinely measured as a clinical marker for diagnosing bone metabolism disorders.
[6]
An overview of osteocalcin progress - PubMed
An increasing amount of data indicate that osteocalcin is an endocrine hormone which regulates energy metabolism, male fertility and brain development.
[7]
BGLAP - Osteocalcin - Homo sapiens (Human) | UniProtKB | UniProt
Osteocalcin is a bone protein that acts as a negative regulator of bone formation and a hormone that regulates energy metabolism, male fertility and brain ...Missing: weight | Show results with:weight
[8]
Bone Control of Muscle Function - MDPI
Osteocalcin (Ocn) is a 49 amino acid polypeptide protein. It is the most abundant noncollagenous protein within the bone matrix, representing about 15%, mainly ...
[9]
Calcium-dependent alpha-helical structure in osteocalcin - PubMed
Osteocalcin exhibits a major conformational change when Ca2+ is bound. Metal-free chicken osteocalcin is a random coil with only 8% of its residues in the alpha ...Missing: beta- sheets motif
[10]
The three-dimensional structure of bovine calcium ion-bound ...
We have solved the three-dimensional structure of calcium bound osteocalcin using (1)H 2D NMR techniques and proposed a mechanism for mineral binding.Missing: beta- sheets
[11]
The structural role of osteocalcin in bone biomechanics and its ...
Oct 14, 2020 · This study presents an investigation into the role of Osteocalcin (OC) on bone biomechanics, with the results demonstrating that the protein's α-helix ...Missing: loop- | Show results with:loop-
[12]
GAMMA-CARBOXYGLUTAMIC ACID PROTEIN, BONE; BGLAP
Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice.<|control11|><|separator|>
[13]
Bone-specific transcription factor Runx2 interacts with the 1alpha,25 ...
The rat OC gene promoter contains three recognition sites for Runx2 (sites A, B, and C). Mutation of sites A and B, which flank the 1alpha,25 ...
[14]
Bglap MGI Mouse Gene Detail - MGI:88156 - bone gamma ...
Symbol. Bglap ; Name. bone gamma carboxyglutamate protein ; Synonyms. Bglap1, bone Gla protein, mOC-A, OC, OG1, osteocalcin ; Feature Type. protein coding gene.
[15]
Expression of osteocalcin and its transcriptional regulators core ...
Osteocalcin is upregulated by the transcription factor core-binding factor alpha 1, which is responsible for commitment to the osteoblastic lineage.
[16]
Overexpression of BMP-2 modulates morphology, growth, and gene ...
Overexpression of BMP-2 significantly stimulated expression of osteocalcin and alkaline phosphatase genes, indicating its role in osteoblastic differentiation.
[17]
Structure of the rat osteocalcin gene and regulation of vitamin D ...
We have demonstrated two factors regulating osteocalcin gene expression. First, a 200-fold increase occurs in normal fetal calvaria osteoblasts producing a ...
[18]
https://pubmed.ncbi.nlm.nih.gov/11900483/
[19]
Osteocalcin: A Multifaceted Bone-Derived Hormone | Annual Reviews
Aug 21, 2023 · Although this review focuses mostly on the regulation of energy metabolism by osteocalcin, it also touches on its other functions. Lastly, it ...
[20]
Current knowledge of bone-derived factor osteocalcin: its role in the ...
Feb 16, 2024 · Impaired bone matrix glycoprotein pattern is associated with ... osteocalcin and osteocalcin levels in postmenopausal osteoporosis. J ...
[21]
New insights into the biology of osteocalcin - ScienceDirect.com
Osteocalcin is a secreted factor influencing matrix mineralization and global metabolism. Osteocalcin regulates glucose metabolism via a bone–pancreas ...
[22]
Vitamin K-Dependent Carboxylation of Osteocalcin: Friend or Foe?
Mar 2, 2012 · In 1974, 2 groups independently isolated a small vitamin K-dependent protein from bone that contained 3 Gla residues and named it Bone Gla ...
[23]
Vitamin K-Dependent Carboxylation of Osteocalcin: Friend or Foe?
In humans, the percentage of the circulating osteocalcin that is not γ ... Serum osteocalcin is correlated with bone formation and osteoblast number as ...
[24]
Undercarboxylated Osteocalcin and Its Associations With Bone ...
Jul 8, 2022 · According to the degree of carboxylation, OC presents in two forms: fully carboxylated OC (cOC) and undercarboxylated OC (ucOC) lacking ...
[25]
Vitamin K Status and Bone Health: An Analysis of Methods for ...
Methods use differences in binding of undercarboxylated and fully carboxylated osteocalcin to hydroxyapatite or barium sulfate. We evaluated these methods ...
[26]
Osteocalcin promotes bone mineralization but is not a hormone
Jun 2, 2020 · One possible explanation for the differences between results in mice and those in humans is that OCN genetics and function differ between humans ...Missing: length rodent
[27]
Osteocalcin induces chemotaxis, secretion of matrix proteins, and ...
Osteocalcin, also called Bone Gla Protein (BGP), is the most abundant of the non-collagenous proteins of bone produced by osteoblasts.
[28]
Increased bone formation in osteocalcin-deficient mice - Nature
Letter; Published: 01 August 1996. Increased bone formation in osteocalcin-deficient mice. Patricia Ducy,; Christelle Desbois,; Brendan Boyce, ...
[29]
Release of intact and fragmented osteocalcin molecules from bone ...
Both rat and human osteoclasts released osteocalcin from bovine bone into medium. The amount of osteocalcin increased in the presence of parathyroid hormone, a ...
[30]
https://pubmed.ncbi.nlm.nih.gov/14970229/
[31]
Osteocalcin Promotes β-Cell Proliferation During Development and ...
Feb 13, 2014 · This study shows that osteocalcin, via Gprc6a, directly controls β-cell proliferation and insulin production but has no overt function in ...Research Design And Methods · Results · Osteocalcin/gprc6a Signaling...
[32]
Association between Serum Osteocalcin and Markers of Metabolic ...
Serum osteocalcin concentration was inversely associated with blood markers of dysmetabolic phenotype and measures of adiposity.
[33]
https://diabetesjournals.org/diabetes/article/63/3/1021/16978/Osteocalcin-Promotes-Cell-Proliferation-During
[34]
Osteocalcin regulates murine and human fertility through a pancreas ...
May 24, 2013 · The osteoblast-derived hormone osteocalcin promotes testosterone biosynthesis in the mouse testis by binding to GPRC6A in Leydig cells.
[35]
Gpr158 mediates osteocalcin’s regulation of cognition | Journal of Experimental Medicine | Rockefeller University Press
### Key Findings on Osteocalcin's Role in Brain Function, Cognition, and Anxiety via GPR158
[36]
https://www.jci.org/articles/view/65952
[37]
The half-life of the bone-derived hormone osteocalcin is regulated ...
Dec 7, 2020 · First, only 30 out of the 46 amino acids (i.e. 65%) composing mature mouse OCN are conserved in human OCN. This is in striking contrast with ...
[38]
Laboratory aspects and clinical utility of bone turnover markers - PMC
Although produced by the osteoblasts, osteocalcin may be defined as a bone turnover marker reflecting both bone formation and bone resorption, since it is also ...Markers Of Bone Turnover · Biomarkers Of Bone... · Biomarkers Of Bone Formation
[39]
Bone Turnover Markers: Basic Biology to Clinical Applications
The immature osteoblast synthesizes alkaline phosphatase and type I collagen whereas the mature osteoblast synthesizes osteocalcin. ... binds to integrins ...
[40]
[PDF] REVIEW MEMORANDUM - FDA
The Elecsys N-MID Osteocalcin Assay is a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. Results are.
[41]
Osteocalcin and its forms across the lifespan in adult men - PubMed
Results: The normal ranges for young men (≤30 years) were: tOC 17.9-56.8 ng/mL, ucOC 7.1-22.0 ng/mL, cOC 8.51-40.3 ng/mL (2.5th to 97.5th quantiles). Aging was ...
[42]
Evaluation of serum osteocalcin as an index of altered bone ...
In the controls serum osteocalcin was higher in children less than 15 years (median and range: 11.9, 7.7-15.3 ng/ml) than in adults (3.7, 2.6-5.2 ng/ml) and ...
[43]
Reference intervals for serum osteocalcin concentrations in adult ...
Mar 13, 2013 · Median (1st-3rd quartile) serum OC concentrations were 15.4 ng/mL (12.0-19.4 ng/mL) in men, 14.4 ng/mL (11.3-18.5 ng/mL) in premenopausal women, ...
[44]
Correlation of Undercarboxylated Osteocalcin (ucOC) Concentration ...
Jul 21, 2010 · Undercarboxylated osteocalcin (ucOC) has been used as hip fracture indicator, since it is related to vitamin K and the observed amount of ucOC ...<|control11|><|separator|>
[45]
Pronounced Elevation of Undercarboxylated Osteocalcin in Healthy ...
Osteocalcin is a bone Gla protein and synthesized by osteoblasts (3). ... To adequately carboxylate osteocalcin, the osteoblast requires sufficient vitamin K ( ...Results · Subjects · Vitamin K Status Of Bone
[46]
The Treatment and Monitoring of Osteoporosis using Bone Turnover ...
Jan 6, 2025 · Bone turnover markers serve as important biological tools in the treatment and monitoring of osteoporosis that are becoming more popular in the clinical world.Formation Markers · Resorption Markers · Evaluation Of Markers
[47]
Osteocalcin in human serum: a circadian rhythm - PubMed - NIH
Osteocalcin levels fell during the morning, rose in the afternoon and early evening, and reached a peak nocturnally.Missing: adults | Show results with:adults
[48]
Bone turnover markers - RACGP
Bone resorption markers typically fall by over 40% within 3 months of starting bisphosphonate therapy. This is followed by a reduction in bone formation markers ...
[49]
Test ID: OSCAL Osteocalcin, Serum
By means of osteocalcin measurements, it is possible to monitor therapy with antiresorptive agents (bisphosphonates or hormone replacement therapy) in, for ...
[50]
Association between Osteocalcin, Metabolic Syndrome, and ...
Undercarboxylated osteocalcin (uOC) regulates insulin secretion and sensitivity in mice, but its relation to MetS in humans is unclear. We aimed to determine ...
[51]
Circulating Undercarboxylated Osteocalcin as Estimator of ... - Nature
Feb 4, 2020 · Undercarboxylated osteocalcin (ucOC) could be a biomarker of glucose disturbances and cardiovascular risk. Our study aimed to determine the ...
[52]
Undercarboxylated Osteocalcin: Experimental and Human Evidence ...
Epidemiological studies associate lower circulating concentrations of undercarboxylated osteocalcin, or a lower ratio of undercarboxylated to total ...
[53]
Undercarboxylated osteocalcin does not correlate with insulin ...
Dec 18, 2012 · We found no significant correlation between ucOC levels and insulin resistance in patients with type 2 diabetes. These findings suggest that it ...
[54]
OSCAL - Overview: Osteocalcin, Serum - Mayo Clinic Laboratories
Osteocalcin levels are increased in metabolic bone diseases with increased bone or osteoid formation, including osteoporosis, osteomalacia, rickets, ...
[55]
Serum osteocalcin levels in primary hyperparathyroidism
The serum levels of osteocalcin were elevated in 22 patients (55%), whereas the serum levels of alkaline phosphatase were increased in 18 patients (45%). In 10 ...Missing: total metastases osteodystrophy
[56]
Diagnosis of renal osteodystrophy among chronic kidney disease ...
Feb 12, 2009 · In conclusion, we found that on a collective basis serum levels of PTH, AP, bsALP, and osteocalcin are high in highturnover bone disease and low ...
[57]
Causal effect of blood osteocalcin on the risk of Alzheimer's disease ...
May 20, 2024 · Clinical studies have shown that individuals with osteopenia or osteoporosis are at a higher risk of developing AD [43, 44]. Moreover, lower ...
[58]
The Role of Bone-Derived Osteocalcin in Testicular Steroidogenesis
It was first isolated and characterised by Hauschka and Price in the 1970s [17,18]. This small protein makes up approximately 1% of the total body protein ...
[59]
Osteocalcin Levels in Male Idiopathic Hypogonadotropic ... - Frontiers
Evidence from mouse and human studies has demonstrated that OC can regulate male fertility through promoting testosterone biosynthesis by Leydig cells, thus ...Missing: 2024 | Show results with:2024
[60]
Vitamin K and Bone Health: A Review on the Effects of Vitamin ... - NIH
Dec 31, 2019 · Studies exploring the relationship between vitamin K supplementation and fracture risk also find that the risk of fracture is reduced with ...
[61]
Gpr158 mediates osteocalcin's regulation of cognition - PMC
That osteocalcin (OCN) is necessary for hippocampal-dependent memory and to prevent anxiety-like behaviors raises novel questions. One question is to determine ...