The Phosphoinositide 3-Kinase Isoform PI3Kβ Regulates Osteoclast-Mediated Bone Resorption in Humans and Mice

Objective. While phosphoinositide 3-kinases (PI3Ks) are involved in various intracellular signal transduction processes, the specific functions of the different PI3K isoforms are poorly understood. We have previously shown that the PI3K isoform is required for arthritis development in the K/BxN serum–transfer model. Since osteoclasts play a critical role in pathologic bone loss during inflammatory arthritis and other diseases, we undertook this study to test the role of PI3K in osteoclast development and function using a combined genetic and pharmacologic approach. Methods. The role of PI3K in primary human and murine osteoclast cultures was tested with the PI3K-selective inhibitor TGX221 and by using PI3K / mice. The trabecular bone architecture of PI3K / mice was evaluated using micro–computed tomography and histomorphometric analyses.