Bone Abstracts

Osteoporosis is an age related disease characterised by a progressive decrease of bone mineral density and loss of bone quality. Twin studies show that genetic component contributes up to 85% of the BMD variability of population. Surprisingly little variability of BMD can be explained by genetic polymorphisms (~2.9%). This highlights the complex genetic architecture and suggests that many other molecular processes and genes have to be involved. Our previous research showed that ADRA2A is deregulated in osteoporotic bone osteoblasts in comparison to osteoartrotic bone osteoblasts. In addition, it has been known for some time that adrenergic stimulation results in osteoclast differentiation leading to bone resorption. There are numerous evidences that this happens through adrenergic receptor β2 (ARβ2) signalling. The same role is apparently performed by two other AR (ADRA2A and ADRA2C). Double AR knock-out female mice have a high bone mass phenotype. Additionally, it has been shown that such mice also exhibit lower tartrate-resistant acid phosphatase (TRACP) and receptor activator of NF-κB (RANK). In order to show that ADRA2A could be involved in bone turnover in men its expression and methylation in bone cells were investigated. Expression of ADRA2A was investigated using immunohistochemistry. Methylation analysis of ADRA2A promoter region was performed on DNA samples isolated from 65 individuals using high resolution melting (HRM) curve analysis, single strand conformation analysis (SSCA) and automatic sequencing. The results show that ADRA2A is expressed by osteoblasts and lining cells but not osteocytes. Methylation analysis did not reveal methylation of ADRA2A promoter DNA. The study showed that ADRA2A may play important role in adrenergic signalling in osteoblasts and lining cells. Although ADRA2A promoter is rich with CpGs and therefore a good target for repression by methylation, other mechanisms must be responsible for ADRA2A repression in osteocytes.