Anales RANF

P.96 PANNEXIN1 KO MICE ARE IRRESPONSIVE TO TENOFOVIR INDUCED BONE LOSS Ane Larrañaga-Vera a , Francisco M Conesa-Buendía b , Bruce N Cronstein a , Aranzazu Mediero a,b a Division of Translational Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA. b Bone and Joint Research Unit, IIS-Fundación Jiménez Díaz UAM, Madrid, Spain. Introduction: Tenofovir is anti-retroviral agent prescribed to human immunodeficiency virus (HIV) patients as part of the drug regimen known as highly active anti-retroviral therapy (HAART). Tenofovir also causes osteopenia resulting in pathological fractures and hospitalisation in these patients. This is now increasingly significant since tenofovir is one of the components of HIV pre-exposure prophylaxis, wich is available for the population at risk. Currently there are not many studies in this regard but several authors has reported that this population also suffers a decrease in BMD. A recently published study suggests that this is caused by a reduction of extracellular adenosine produced by Tenofovir mediated blockage of Pannexin-1 ATP transporter and this effect can be reversed by dipyridamole that blocks adenosine re-uptake. To further confirm this study Pannexin-1 KO (PANX1KO) mice were studied and compared to C57BL/6J (WT) mice. Methods: PANX1KO animals were treated daily with 75mg/Kg of tenofovir, 25  mg/kg tenofovir or both during 4 weeks, after that bone mineral density (BMD) was measured. Additionally primary osteoclasts were differentiated and treated with different concentrations of Tenofovir and dipyridamole. The differentiation stage and extracellular ATP levels were studied. Results: In WT mice Tenofovir caused a reduction bone mineral density and this was reversed in the animals who received both drugs. However PANX1KO mice that receive Tenofovir did not present a lower BMD. In WT mice Dipyridamole inhibited osteoclast differentiation (p= 0.0068). The dipyridamole induced inhibition was reverted with Tenofovir in a dose dependent manner (0.0055). PANX1KO mice osteoclast differentiation was also inhibited by dipyridamole (p=0.0005), however Tenofovir was unable to revert dipyridamole induced inhibition (p= 0.9756). Additionally, opposed to the WT osteoclasts, PAX1KO mice did not decrease ATP release when treated with Tenofovir (p= 0.3292). Conclusion: In the absence of pannexin-1 transporter tenofovir is not able to influence BMD or osteoclast differentiation.