Hormone Relaxin as Biomarker for Bone Health and Disease

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


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.


Bone Relaxin Relaxin family peptide receptor Osteoblast Osteoclast Bone remodeling Collagen 

List of Abbreviations


Alkaline phosphatase


Bone-specific alkaline phosphatase


Bone collagen equivalents


Bone morphogenetic protein


Basic multicellular unit


Bone sialoprotein


Bone turnover marker


Cyclic adenosine monophosphate


Colony-stimulating factor 1 receptor


Chemiluminescence immunoassay


Collagen type I alpha 1


Urinary creatinine


Carboxy-terminal cross-linking telopeptide of type 1 collagen




Dual-energy X-ray absorptiometry


Electrochemiluminescence immunoassay


Extracellular signal-regulated kinase


Fibroblast growth factor


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


Insulin-like growth factor-1


Insulin-like peptide


Macrophage colony-stimulating factor


Matrix metalloproteinase


Messenger RNA


Nuclear factor of activated T-cells cytoplasmic 1


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


Amino-terminal mid-fragment


Nitric oxide


Amino-terminal cross-linking telopeptide of type 1 collagen








Peripheral blood monocyte cells


Periodontal ligament


Carboxy-terminal propeptide of type 1 collagen


Amino-terminal propeptide of type 1 collagen


Parathyroid hormone




Receptor activator of NF-kB


Receptor activator of NF-kappaB ligand



RLN (Rln)



Runt-related transcription factor 2

RXFP (Rxfp)

Relaxin family peptide receptor


Soluble RANKL


Transforming growth factor-β


Tartrate-resistant acid phosphatase


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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