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ADRA2A is involved in neuro-endocrine regulation of bone resorption
Mlakar, Vid (Author), Marc, Janja (Author), Preželj, Janez (Author), Zupan, Janja (Author), Jurković Mlakar, Simona (Author), Komadina, Radko (Author)

URLURL - Presentation file, Visit http://onlinelibrary.wiley.com/doi/10.1111/jcmm.12505/full This link opens in a new window

Abstract
Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through [alpha]2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of [alpha]2A-AR in bone. The aim of this study was to investigate the presence of [alpha]2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate [alpha]2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in [alpha]2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-timePCR, genetic association study between rs553668 A>G and rs1800544 C>GSNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. [alpha2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on [alpha]2A-AR mRNA level in human bone samples through the stability of mRNA. [alpha]2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that [alpha]2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in [alpha]2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis.

Language:English
Keywords:osteoblasti, resorpcija, adrenergični receptorji alfa, ADRA2A
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Year:2015
Number of pages:str. 1520-1529
Numbering:Vol. 19, issue 7
UDC:577:616.71-007.234
ISSN on article:1582-4934
DOI:10.1111/jcmm.12505 Link is opened in a new window
COBISS.SI-ID:3887217 Link is opened in a new window
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Downloads:260
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Record is a part of a journal

Title:Journal of Cellular and Molecular Medicine
Shortened title:J. Cell. Mol. Med.
Publisher:University Press "Carol Davila"
ISSN:1582-4934
COBISS.SI-ID:519151385 This link opens in a new window

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