Osteocalcin(OCN), aka Bone Gla Protein(BGP), is a non-collagenous acidic glycoprotein composed of 49 amino acids that is synthesized mainly by osteoblasts and odontoblasts, and is one of the most abundant non-collagenous proteins in bone. The “Gla” in its name comes from the γ-carboxyglutamic acid residue, a structure that allows osteocalcin to bind calcium ions and participate directly in the mineralization process of bone, maintaining bone strength and hardness.
 

Osteocalcin | Basic Properties

Molecular Structure: OCN consists of 49 amino acids and contains 3 carboxyglutamic acid residues (γ-carboxyglutamic acid), which enable it to bind hydroxyapatite and calcium.
Source: OCN is mainly synthesized and secreted by osteoblasts and odontoblasts, and is essential for mineralization of the bone matrix.
Classification: According to the degree of carboxylation, OCN is classified into cOCN and ucOCN. cOCN is mainly deposited in the bone matrix, while ucOCN acts through the blood circulation.
 

Form	Carboxylation Status	Calcium Affinity	Function
cOCN	Fully carboxylated	High	Bone matrix mineralization
ucOCN	Uncarboxylated	Low	Endocrine regulation

 

Osteocalcin | 3 Core Functions

The “Architect” of Bones
Osteocalcin is a key regulator of bone formation, which can stimulate the proliferation and differentiation of osteoblasts to promote new bone production, while inhibiting osteoclast activity to reduce bone loss and maintain bone stability.
 
The “Balancer” of Calcium and Phosphorus Metabolism
By regulating intestinal calcium absorption and renal calcium excretion, it maintains stable blood calcium levels and prevents osteoporosis and abnormal mineralization.
 
The “Invisible Conductor” of the Metabolic System
Recent studies have found that uncarboxylated osteocalcin (ucOC) can act as a hormone in the pancreas, adipose, muscle and other organs, promoting insulin secretion, enhancing insulin sensitivity, regulating lipocalin levels, and even affecting energy metabolism and reproductive function.  

Osteocalcin | Genes and Expression

Gene Location and Structure
The human osteocalcin gene is located on chromosome 1, 1q25 to q31, and encodes a 98 amino acid precursor protein. Mice contain 3 ocn gene clusters. The structure of the osteocalcin gene is relatively conserved between species, but some differences exist between species. For example, the promoter region of the human osteocalcin gene differs from that of the mouse osteocalcin gene in terms of sequence and transcription factor binding sites, which may affect its expression pattern and regulatory mechanism in different species.
 
Expression Regulation
Osteocalcin expression is regulated by a variety of factors. Hormones such as vitamin D, parathyroid hormone (PTH), and glucocorticoids, as well as physical factors such as mechanical stress, can affect osteocalcin expression. For example, vitamin D can regulate the transcription of the osteocalcin gene by binding to the vitamin D receptor, thereby affecting osteocalcin synthesis and secretion. In addition, osteocalcin expression is also regulated by local growth factors and cytokines, such as transforming growth factor-β (TGF-β) and insulin-like growth factor (IGF), which regulate osteocalcin expression by activating different signaling pathways.
 

Osteocalcin | Signal Pathway

Wnt/β-catenin Signaling Pathway
Osteocalcin promotes osteoblast proliferation and differentiation through activation of the Wnt/β-catenin signaling pathway, which in turn accelerates the synthesis of bone matrix. In this process, osteocalcin may activate the Wnt signaling pathway by interacting with Wnt ligands or regulating key molecules in the Wnt signaling pathway. Activation of the Wnt signaling pathway stabilizes β-catenin protein, allowing it to accumulate in the cytoplasm and enter the nucleus, where it binds to the transcription factor TCF/LEF and regulates the expression of downstream target genes, such as RUNX2, thereby promoting osteoblast differentiation and bone formation.
 
PPARγ Signaling Pathway
Osteocalcin is also able to regulate adipocyte metabolism and function by activating the PPARγ signaling pathway. Uncarboxylated osteocalcin (ucOCN) can bind to GPRC6A receptors and activate downstream signaling pathways, leading to PPARγ activation. PPARγ is a major regulator of adipogenesis, and its activation can increase the expression of adipokines such as lipocalin, thereby improving insulin sensitivity and energy metabolism. In addition, osteocalcin regulates adipocyte differentiation and lipid storage through the PPARγ signaling pathway, which is important for maintaining systemic energy homeostasis.
 
Akt Signaling Pathway
Osteocalcin binds to and activates the osteocalcin receptor on osteoblasts, triggering an intracellular cascade that leads to the activation of the Akt signaling pathway. Activation of the Akt signaling pathway promotes the proliferation and survival of osteoblasts and inhibits apoptosis. In addition, the Akt signaling pathway is involved in the regulation of osteoblast differentiation and function, which is important for bone formation and bone mass maintenance.
 
RANK/RANKL/OPG Signaling Pathway
Osteocalcin is also involved in the activation of the RANK/RANKL/OPG signaling pathway, which plays a key role in osteoclast differentiation and function. By regulating the expression of RANKL and OPG, osteocalcin is able to influence osteoclast production and activity, thereby regulating the process of bone resorption. This regulatory effect is coordinated with the role of osteocalcin in osteoblasts, and together they maintain the dynamic balance of bone tissue.
 

Osteocalcin | Research Progress

Differences in carboxylated forms: Studies have shown that there are differences in the functions of cOCN and ucOCN in different tissues. cOCN is mainly involved in bone matrix mineralization, whereas ucOCN regulates energy metabolism and other systemic functions through blood circulation.
Associations with other diseases: OCN levels are negatively correlated with aging and have also shown important roles in aging-related diseases and exercise stress response.
 

General Biochemical Indicators	Blood calcium, urine calcium, blood phosphorus, urine phosphorus
Bone Metabolism-regulating Hormone	Parathyroid Hormone(PTH)
	1,25-(OH)2D
Bone Transformation Indicators	Bone Formation Indicators	ALP
		BGP
		PINP
	Bone Resorption Indicators	CTX
		DPD
		TRAP-5b

Osteocalcin is a multifunctional bone-derived hormone, that not only plays a key role in bone metabolism, but also has a wide range of influences in energy metabolism, endocrine regulation, and nervous system function. Its use as a biomarker is valuable in the study of bone metabolic diseases, diabetes, and obesity. Future studies will further reveal the specific mechanisms of OCN in different tissues and its potential applications in disease treatment.
 

Jonlnbio | Osteocalcin Hot-selling Indicators

JL19437 Human Osteocalcin (BGP;OCN) ELISA Kit
JL21019 Rat Osteocalcin (BGP;OCN) ELISA Kit
JL20366 Mouse Osteocalcin (BGP;OCN) ELISA Kit
 

 Jonlnbio | Osteocalcin Citations