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Hormone Relaxin as Biomarker for Bone Health and Disease

  • Yukiho KobayashiEmail author
  • Carolina DuarteEmail author
  • Keiji MoriyamaEmail author
Reference work entry
  • 843 Downloads
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series (BDMDA)

Abstract

Bone homeostasis is maintained by fine-tuning of the dynamic balance between bone resorption via osteoclasts and bone formation via osteoblasts. Bone metabolism-related biomarkers such as a soluble factor or type I collagen metabolism product specifically secreted by osteoblasts or osteoclasts are useful for evaluating the change in bone metabolism in a noninvasive manner in real time. Monitoring of bone metabolism-related biomarkers that are excreted in the urine or secreted into the bloodstream is quite useful for the diagnosis of various kinds of skeletal metabolism abnormalities. For example, an elevated level of a bone metabolism marker is a risk factor of bone fracture independent of bone density, as well as for bone density loss in the future. Relaxin (RLN) is a pleiotropic hormone of the insulin-like peptide hormone family, which is mainly secreted into the bloodstream from the ovary, uterus, and placenta during pregnancy. Therefore, RLN helps labor to progress by softening and widening the pubic symphysis and cervix, owing to its ability of remodeling the extracellular matrix by degrading collagen. The physiological roles of RLNs and relaxin family peptides through their receptors, relaxin family peptide receptors (RXFPs), in the reproductive system have been extensively studied. However, recent studies have shown that RLNs/RXFPs also play a key role in the cardiovascular system, renal function, organ protection, metabolism, cancer metastasis, and the central nervous system. The effectiveness of RLN for the treatment of acute heart failure is now assessed under phase III clinical trials. In addition to these broad physiological activities, its role in bone metabolism was also recently highlighted because of its ability to induce osteoclastogenesis, activate osteoclast function, and enhance osteoblast differentiation in vitro. In addition, the majority of men with RXFP2 mutations presented with symptoms of osteoporosis, and Rxfp2-deficient mice showed a lower bone mass and reduced osteoclast surface compared to their wild-type littermates. This chapter provides an overview of the biological functions of RLN and its receptors (RXFPs), with particular focus on bone metabolism. In addition, the utility and possibility of RLNs/RXFPs as biomarkers for bone health and disease are discussed.

Keywords

Bone Relaxin Relaxin family peptide receptor Osteoblast Osteoclast Bone remodeling Collagen 

List of Abbreviations

ALP

Alkaline phosphatase

BAP

Bone-specific alkaline phosphatase

BCE

Bone collagen equivalents

BMP

Bone morphogenetic protein

BMU

Basic multicellular unit

BSP

Bone sialoprotein

BTM

Bone turnover marker

cAMP

Cyclic adenosine monophosphate

c-FMS

Colony-stimulating factor 1 receptor

CLIA

Chemiluminescence immunoassay

COL1α1

Collagen type I alpha 1

CREA

Urinary creatinine

CTX

Carboxy-terminal cross-linking telopeptide of type 1 collagen

DPD

Deoxypyridinoline

DXA

Dual-energy X-ray absorptiometry

ECLIA

Electrochemiluminescence immunoassay

ERK

Extracellular signal-regulated kinase

FGF

Fibroblast growth factor

ICTP

Carboxy-terminal cross-linking telopeptide of type 1 collagen generated by MMPs

IGF-1

Insulin-like growth factor-1

INSL

Insulin-like peptide

M-CSF

Macrophage colony-stimulating factor

MMPs

Matrix metalloproteinase

mRNA

Messenger RNA

NFATc1

Nuclear factor of activated T-cells cytoplasmic 1

NF-kB

Nuclear factor kappa-light-chain-enhancer of activated B cells

N-MID

Amino-terminal mid-fragment

NO

Nitric oxide

NTX

Amino-terminal cross-linking telopeptide of type 1 collagen

OC

Osteocalcin

OPG

Osteoprotegerin

OPN

Osteopontin

PBMC

Peripheral blood monocyte cells

PDL

Periodontal ligament

PICP

Carboxy-terminal propeptide of type 1 collagen

PINP

Amino-terminal propeptide of type 1 collagen

PTH

Parathyroid hormone

PYD

Pyridinoline

RANK

Receptor activator of NF-kB

RANKL

Receptor activator of NF-kappaB ligand

RIA

Radioimmunoassay

RLN (Rln)

Relaxin

RUNX2

Runt-related transcription factor 2

RXFP (Rxfp)

Relaxin family peptide receptor

sRANKL

Soluble RANKL

TGF-β

Transforming growth factor-β

TRAP

Tartrate-resistant acid phosphatase

TRAP5b

Tartrate-resistant acid phosphatase type 5b

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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Department of Maxillofacial Orthognathics, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan
  2. 2.RAK College of Dental SciencesRAK Medical and Health Sciences UniversityRas Al KhaimahUnited Arab Emirates

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