Abstract
Osteocalcin is the most abundant noncollagenous protein of bone matrix. Once transcribed, this protein undergoes posttranslational modifications within osteoblastic cells before its secretion, including the carboxylation of three glutamic residues in glutamic acid, which is essential for hydroxyapatite binding and deposition in the extracellular matrix of bone. Recent provocative data from experimental observations in mice showed that the circulating undercarboxylated fraction of osteocalcin increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral fat in both genders, while it enhances testosterone production by the testes in males. Moreover, both total and undercarboxylated osteocalcins increase following physical activity with potential positive effects on glucose tolerance. Despite that these evidences have been only in part confirmed in humans, further prospective investigations are needed to definitively establish the endocrine role of osteocalcin both in the general population and cohorts of patients with diabetes or other metabolic disorders.
Highlights
Osteocalcin, known as “bone gamma-carboxyglutamic acid (Gla) protein (BGP),” is the most abundant noncollagenous protein of bone matrix [1]
Levels of undercarboxylated osteocalcin are influenced by vitamin K status, whereas total circulating concentrations of osteocalcin are influenced by bone cells activity independent of vitamin K [6]
Even though these posthoc studies provided evidence that bone antiresorptive treatment for up to 4 years does not have major effects on glucose metabolism in postmenopausal women with osteoporosis, this information needs to be replicated on a prospective basis as well as in patients with diabetes or impaired glucose tolerance
Summary
Osteocalcin, known as “bone gamma-carboxyglutamic acid (Gla) protein (BGP),” is the most abundant noncollagenous protein of bone matrix [1] It is a product of differentiated osteoblasts, formed by 46 to 50 amino acids related to species [2,3,4]. Various growth factors, hormones, or cytokines can modulate osteocalcin production through signaling pathways or interacting with transcription factors that act on osteocalcin gene promoter region (BGLAP gene in chromosome 1q25–q31) [4] This gene is generally inactivated during osteoblast proliferation, while it is abundantly transcribed during osteoblast differentiation. Different experimental studies demonstrated that osteocalcin promotes the recruitment and differentiation of circulating monocytes and osteoclast precursors, suggesting its role on osteoblast-osteoclast interaction and bone resorption [2, 4, 7, 8]. Experimental studies on mice models with osteoblast-specific overexpression or downregulation of osteocalcin production suggested that this protein might have an important endocrine function, outside bone, by regulating glucose and lipid homeostasis and probably the production of testosterone by the testes [10,11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
