ADRA2A is involved in neuro-endocrine regulation of bone resorption

作者：Mlakar Vid; Mlakar Simona Jurkovic; Zupan Janja; Komadina Radko; Prezelj Janez; Marc Janja^*

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2015, 19(7): 1520-1529.

DOI：10.1111/jcmm.12505

• ADRA2A
• osteoporosis
• bone
• resorption
• osteoblast
• adrenergic signalling

Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through 2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of 2A-AR in bone. The aim of this study was to investigate the presence of 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 2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in 2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. 2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on 2A-AR mRNA level in human bone samples through the stability of mRNA. 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 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 2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis.

• 出版日期2015-7