Skeletal Endocrinology: Where Evolutionary Advantage Meets Disease

Overview

Journal Bone Res

Specialties Endocrinology
Orthopedics

Date 2021 May 29

PMID 34050126

Citations 5

Authors

Nikolai Jaschke

Wolfgang Sipos

Lorenz C Hofbauer

Tilman D Rachner

Martina Rauner

Affiliations

Soon will be listed here.

Abstract

The regulation of whole-body homeostasis by the skeleton is mediated by its capacity to secrete endocrine signaling molecules. Although bone-derived hormones confer several adaptive benefits, their physiological functions also involve trade-offs, thus eventually contributing to disease. In this manuscript, we discuss the origins and functions of two of the best-studied skeletal mediators, fibroblast growth factor 23 and osteocalcin, in an evolutionary context. Moreover, we provide a theoretical framework seeking to explain the broad involvement of these two hormones in amniote physiology as well as their potential to fuel the development and progression of diseases. Vice versa, we outline which perturbations might be amenable to manipulation of these systems and discuss limitations and ongoing challenges in skeletal endocrine research. Finally, we summarize unresolved questions and potential future studies in this thriving field.

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References

Xiao Z, King G, Mancarella S, Munkhsaikhan U, Cao L, Cai C . FGF23 expression is stimulated in transgenic α-Klotho longevity mouse model. JCI Insight. 2019; 4(23). PMC: 6962016. DOI: 10.1172/jci.insight.132820. View

Dinarello C . Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2017; 281(1):8-27. PMC: 5756628. DOI: 10.1111/imr.12621. View

Murshed M, Schinke T, McKee M, Karsenty G . Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins. J Cell Biol. 2004; 165(5):625-30. PMC: 2172384. DOI: 10.1083/jcb.200402046. View

Wellendorph P, Brauner-Osborne H . Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor. Gene. 2004; 335:37-46. DOI: 10.1016/j.gene.2004.03.003. View

Du J, Zhang M, Lu J, Zhang X, Xiong Q, Xu Y . Osteocalcin improves nonalcoholic fatty liver disease in mice through activation of Nrf2 and inhibition of JNK. Endocrine. 2016; 53(3):701-9. DOI: 10.1007/s12020-016-0926-5. View

Griesshammer M, Kiladjian J, Besses C . Thromboembolic events in polycythemia vera. Ann Hematol. 2019; 98(5):1071-1082. PMC: 6469649. DOI: 10.1007/s00277-019-03625-x. View

Musgrove J, Wolf M . Regulation and Effects of FGF23 in Chronic Kidney Disease. Annu Rev Physiol. 2019; 82:365-390. DOI: 10.1146/annurev-physiol-021119-034650. View

Ito N, Wijenayaka A, Prideaux M, Kogawa M, Ormsby R, Evdokiou A . Regulation of FGF23 expression in IDG-SW3 osteocytes and human bone by pro-inflammatory stimuli. Mol Cell Endocrinol. 2014; 399:208-18. DOI: 10.1016/j.mce.2014.10.007. View

Jorgensen S, Have C, Underwood C, Johansen L, Wellendorph P, Gjesing A . Genetic Variations in the Human G Protein-coupled Receptor Class C, Group 6, Member A (GPRC6A) Control Cell Surface Expression and Function. J Biol Chem. 2016; 292(4):1524-1534. PMC: 5270492. DOI: 10.1074/jbc.M116.756577. View

10.

Persson P . Physiological regulation of renal blood flow and glomerular filtration rate by the endothelium and smooth muscle. Blood Purif. 1997; 15(4-6):219-27. DOI: 10.1159/000170339. View

11.

Akhabue E, Montag S, Reis J, Pool L, Mehta R, Yancy C . FGF23 (Fibroblast Growth Factor-23) and Incident Hypertension in Young and Middle-Aged Adults: The CARDIA Study. Hypertension. 2018; 72(1):70-76. PMC: 6002950. DOI: 10.1161/HYPERTENSIONAHA.118.11060. View

12.

Briggs D . The Cambrian explosion. Curr Biol. 2015; 25(19):R864-8. DOI: 10.1016/j.cub.2015.04.047. View

13.

Jaacks L, Vandevijvere S, Pan A, McGowan C, Wallace C, Imamura F . The obesity transition: stages of the global epidemic. Lancet Diabetes Endocrinol. 2019; 7(3):231-240. PMC: 7360432. DOI: 10.1016/S2213-8587(19)30026-9. View

14.

Benet-Pages A, Lorenz-Depiereux B, Zischka H, White K, Econs M, Strom T . FGF23 is processed by proprotein convertases but not by PHEX. Bone. 2004; 35(2):455-62. DOI: 10.1016/j.bone.2004.04.002. View

15.

Oury F, Khrimian L, Denny C, Gardin A, Chamouni A, Goeden N . Maternal and offspring pools of osteocalcin influence brain development and functions. Cell. 2013; 155(1):228-41. PMC: 3864001. DOI: 10.1016/j.cell.2013.08.042. View

16.

Li L, Li X, Zhou W, Messina J . Acute psychological stress results in the rapid development of insulin resistance. J Endocrinol. 2013; 217(2):175-84. PMC: 3804337. DOI: 10.1530/JOE-12-0559. View

17.

Morelli A, Sarchielli E, Comeglio P, Filippi S, Vignozzi L, Marini M . Metabolic syndrome induces inflammation and impairs gonadotropin-releasing hormone neurons in the preoptic area of the hypothalamus in rabbits. Mol Cell Endocrinol. 2013; 382(1):107-119. DOI: 10.1016/j.mce.2013.09.017. View

18.

Farrow E, Yu X, Summers L, Davis S, Fleet J, Allen M . Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc Natl Acad Sci U S A. 2011; 108(46):E1146-55. PMC: 3219119. DOI: 10.1073/pnas.1110905108. View

19.

Bhattacharyya N, Chong W, Gafni R, Collins M . Fibroblast growth factor 23: state of the field and future directions. Trends Endocrinol Metab. 2012; 23(12):610-8. PMC: 3502714. DOI: 10.1016/j.tem.2012.07.002. View

20.

Kuro-O M . A potential link between phosphate and aging--lessons from Klotho-deficient mice. Mech Ageing Dev. 2010; 131(4):270-5. PMC: 2862786. DOI: 10.1016/j.mad.2010.02.008. View