Endocrine Abstracts

Trans-differentiation of osteoblasts to adipocytes may in part be responsible for diseases such as osteoporosis and arthritis. The processes involved are however complex and largely unknown. Our previous data showed that the adenosine A2b receptor (A2bR) is important for human osteoprogenitor cell function. In this study, we investigated the expression of adenosine receptors in an osteoblast cell line (7F2) and during its differentiation into adipocytes (7F2A).

Oil Red O and Nile Red coupled with FACS analysis showed that 45% of cells in the 7F2A cultures contained lipid after 7 days of induced adipogenesis; such cells were undetectable in 7F2 cultures. Adipogenesis was accompanied with the loss of adenosine or NECA (universal adenosine receptor agonist) induced cAMP responses, at 100 μM, the stimulations were respectively 1900±400 and 3900±300 for 7F2 cells (P<0.001) and 500±200 and 300±60 fmol/ml for 7F2A cells (P<0.001). Induced adipogenesis was also associated with increased A1 receptor (A1R) and decreased A2a receptor (A2aR) and A2bR expression. In 7F2A cells, A1R mRNA increased up to 1500 fold (P<0.001) and that for A2aR and A2bR decreased by up to 70% (P<0.001) when compared with expression in 7F2 cells. On adipogenesis, A1R and A2aR proteins paralleled changes in mRNA and the A2bR protein showed increased phosphorylation.

Stable transfection of human A1R into 7F2 cells induced adipogenesis (20–30%, P<0.001) as determined by Oil Red O staining and Nile Red labelling and increased expression of the adipogenic markers, lipoprotein lipase and glycerol 3-phosphate dehydrogenase. A2bR transfection decreased adipogenesis (20–30%, P<0.001) and increased expression of the osteoblast markers, osteocalcin and alkaline phosphatase with no change in the expression of adipogenic markers.

These data indicate that specific adenosine receptors are important for osteoblast and adipocyte lineage specific differentiation and targeting such pathways may be therapeutically beneficial in those diseases where osteoblastogenesis or adipogenesis is imbalanced.