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Hormone Relaxin as Biomarker for Bone Health and Disease

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Biomarkers in Bone Disease

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.

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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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Authors and Affiliations

  1. Department of Maxillofacial Orthognathics, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8549, Tokyo, Japan

    Yukiho Kobayashi & Keiji Moriyama

  2. RAK College of Dental Sciences, RAK Medical and Health Sciences University, Al Qusaidat, Ras Al Khaimah, United Arab Emirates

    Carolina Duarte

Authors
  1. Yukiho Kobayashi
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  2. Carolina Duarte
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  3. Keiji Moriyama
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Correspondence to Yukiho Kobayashi , Carolina Duarte or Keiji Moriyama .

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Editors and Affiliations

  1. Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

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Kobayashi, Y., Duarte, C., Moriyama, K. (2015). Hormone Relaxin as Biomarker for Bone Health and Disease. In: Preedy, V. (eds) Biomarkers in Bone Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7745-3_12-1

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  • DOI: https://doi.org/10.1007/978-94-007-7745-3_12-1

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