Osteocalcin and Metabolic Regulation in Bone Health
Summary
Osteocalcin, a non-collagenous protein synthesised by osteoblasts, has emerged as a pivotal mediator linking skeletal dynamics with systemic energy metabolism. This protein undergoes γ-carboxylation, a modification that controls its affinity for the bone matrix. The uncarboxylated form circulates as a hormone to potentiate pancreatic β-cell proliferation and insulin secretion, enhance adiponectin expression in adipose tissue and modulate muscle glucose uptake. Concurrently, osteocalcin influences lipid metabolism and energy expenditure, integrating bone remodelling with whole-body glucose and lipid homeostasis. Reciprocal feedback loops, in which insulin receptor signalling in osteoblasts promotes osteocalcin decarboxylation and release, establish an endocrine circuit between bone and traditional metabolic organs. These discoveries have reframed bone as a dynamic endocrine organ, with implications for metabolic regulation, ageing and chronic diseases such as diabetes and osteoporosis.
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Osteocalcin and Metabolic Regulation in Bone Health publication trend
The graph below shows the total number of articles in osteocalcin and metabolic regulation in bone health across all publications each year (not limited to Nature Index journals).
Technical terms
Osteocalcin: A non-collagenous protein produced by osteoblasts that functions as a hormone to regulate energy metabolism and bone quality.
Uncarboxylated osteocalcin (ucOC): The hormonally active form of osteocalcin released into the circulation following decarboxylation, which stimulates insulin secretion and energy expenditure.
Osteoblast: A specialised cell responsible for bone formation and the secretion of osteocalcin.
Bone remodelling: The continuous process of bone formation by osteoblasts and resorption by osteoclasts, essential for skeletal integrity and mineral balance.
Homeostasis: The maintenance of stable internal physiological conditions, including glucose and mineral balance, through coordinated organ-level signalling.
References
- Osteocalcin: A Multifaceted Bone-Derived Hormone. Annual Review of Nutrition (2023).
- Endocrine Regulation of Energy Metabolism by the Skeleton. Cell (2007).
- Hyperglycemia from Diabetes Potentiates Uncarboxylated Osteocalcin-Stimulated Insulin Secretion in Rat INS-1 Pancreatic β-Cells. Nutrients (2024).
- Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring. EMBO Reports (2024).
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