Bone Abstracts

The P2Y₂ receptor is a G-protein-coupled receptor and the natural ligands (ATP/UTP) strongly inhibit mineralized bone nodule formation by osteoblasts in vitro. We have earlier shown that overexpression of the P2Y₂ receptor in vivo resulted in decreased bone mineral density (BMD), partially due to increased bone resorption, but also decreased formation (detected by serum bone markers and bone histomorphometry).

This study, engaging 189 nullipara female P2Y₂ knockout (KO) mice and wild type siblings, can be divided into two sub-studies. The first sub-study examines the impact P2Y₂ gene KO on bone development from birth to nine months of age, with detection of body weight and DEXA BMD every 4th week. In the second sub-study mature animals of both genotypes were divided into groups to study bone loss following estrogen withdrawal and immobilization. These animals were followed for 3 months monitoring paralysis score, body weight and BMD.

P2Y₂-KOs had significantly higher BMD after maturity, for example at the age of 20 weeks the P2Y₂-KOs had a whole-body BMD at 0.0572±0.0007 g/cm² in contrast to 0.0546±0.0009 g/cm², (P=0.002). Two weeks of immobilization decreased femoral BMD with 6–13%, with highest bone loss in P2Y₂-KOs, resulting in no difference between the two genotypes. The same pattern was seen with the ovariectomized animals.

In conclusion these studies confirm the regulatory role of the P2Y₂ receptor in bone remodeling. Furthermore they show the value of pharmaceutical manipulation of the P2Y₂ receptor.