Searching for additional endocrine functions of the skeleton: genetic approaches and implications for therapeutics

Abstract

Our knowledge of whole organism physiology has greatly advanced in the past decades through mouse genetics. In particular, genetic studies have revealed that most organs interact with one another through hormones in order to maintain normal physiological functions and the homeostasis of the entire organism. Remarkably, through these studies many unexpected novel endocrine means to regulate physiological functions have been uncovered. The skeletal system is one example. In this article, we review a series of studies that over the years have identified bone as an endocrine organ. The mechanism of action, pathological relevance, and therapeutic implications of the functions of the bone-derived hormone osteocalcin are discussed. In the last part of this review we discuss the possibility that additional endocrine functions of the skeleton may exist.

Roles of osteoprotegerin in endocrine and metabolic disorders through receptor activator of nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B signaling

“…The main components of a bone include osteoblasts, osteocytes, marrow adipocyte tissue, and mineralized fibrous tissue ( Zhang et al, 2015 ; Lecka-Czernik et al, 2017 ). The RANKL/RANK/OPG system participates in pathological and physiological processes by secreting bone-derived hormones ( Ferron et al, 2008 ; DiGirolamo et al, 2012 ; Wei et al, 2015 ; Zhang et al, 2015 ; Bernardi et al, 2016 ). RANKL can activate RANK in osteoclast precursor cells by residing in bone-forming cells and inducing osteoclastogenesis to promote bone resorption ( Ikebuchi et al, 2018 ).…”

The Expanding Life and Functions of Osteogenic Cells: From Simple Bone-Making Cells to Multifunctional Cells and Beyond

“…This was further illustrated by the finding that fibroblast growth factor 23 (FGF23) produced by osteoblasts and osteocytes acts on kidneys to increase phosphate elimination . It is thus likely that several bone‐derived hormones produced by osteoblasts/osteocytes may contribute to the endocrine functions of the skeleton …”