Osteocalcin—A Versatile Bone-Derived Hormone

Abstract

Bone has long been regarded as a static organ, simply providing protection and support. However, this mindset has changed radically in recent years and bone is becoming increasingly recognized for its endocrine function of secreting several hormones, thereby controlling various physiological pathways. One of the factors released by the skeleton is osteocalcin. Importantly, osteocalcin is secreted solely by osteoblasts but only has minor effects on bone mineralization and density. Instead, it has been reported to control several physiological processes in an endocrine manner, such as glucose homeostasis and exercise capacity, brain development, cognition, and male fertility. The aim of this review is to provide an overview of the currently known roles of osteocalcin and their underlying mechanisms. At present, one of the major goals in this field is translating basic research into therapeutic applications, therefore ongoing efforts to bring these findings to the clinics will also be discussed.

A novel screening test to predict the developmental toxicity of drugs using human induced pluripotent stem cells

“…It reduces the vitamin K redox cycle by inhibiting NAD(P)H-dependent reductase, resulting in the inhibition of the activation of proteins, such as blood coagulation factor in the liver and osteocalcin in the bone tissue (Nelsestuen et al, 1974;Kim et al, 2013;Gallieni and Fusaro, 2014). Osteocalcin is a vitamin K-dependent Cabinding protein involved in bone remodeling (Moser and van der Eerden, 2019). Decreased vitamin K increases the incidence of fractures (Hao et al, 2017).…”

Interactions between Muscle and Bone—Where Physics Meets Biology

“…Bone-specific secreted products can influence the formation, maintenance, and regeneration of muscle and other tissues. Many bone regulating signal transducers such as transforming growth factor β (TGFβ) and the ligands of the wnt pathway are usually thought to act more locally, but wnt3a can influence myoblast differentiation and might also act at a certain distance [76] The most prominent secreted products of bone with endocrine effects are the osteoblast marker proteins osteocalcin and the osteocyte-derived phosphatonin fibroblast growth factor 23 (FGF23) as well as the inhibitors of osteogenic wnt signaling sclerostin (SOST) and Dickkopf-related protein 1 (DKK-1).…”

“…The degree of vitamin K-dependent γ-carboxylation of osteocalcin determines its activity in insulin sensitizing and muscular glucose uptake, where undercarboxylated or uncarboxylated osteocalcin is the most active. The injection of uncarboxylated osteocalcin in mice rescued their exercise capacity and rescued the age-associated loss of muscle mass (reviewed in [76]. G protein-coupled receptor family C group 6 member A (Gprc6a) is the receptor for osteocalcin, and its knockout in mice abolished the effect of uncarboxylated osteocalcin injections, indicating that this effect is specific for Gprc6a/osteocalcin-mediated signal transduction.…”

Zebrafish: An Emerging Model for Orthopedic Research

“…Finally, the skeleton can regulate the metabolic processes independent of mineral metabolism. For instance, the bone‐derived hormone osteocalcin has been implicated in glucose homeostasis, cognition, and male fertility . Whether the zebrafish skeleton functions as an endocrine organ through osteocalcin secretion requires further investigation.…”