Background Local bone destruction in rheumatoid arthritis, proriasisarthritis or ankylosing spondylitis often leads to disability and severely reduced quality of life. This damage to the bony structures is almost exclusively mediated by a special cell type, the osteoclasts. Therefore, it is important to understand factors and pathways regulating the generation of osteoclasts.
Objectives In this study, we analyzed the impact of the PI3-Kinase/PTEN axis on osteoclast generation and bone biology under basal and inflammatory conditions.
Methods Analysis of in vitro osteoclastogenesis and in vitro osteoclast function, bone histomorphometry, qPCR, clinical and histological examination of myeloid specific PTEN-/- crossed into human TNF transgenic mice
Results We show that mice with a monocyte/macrophage-specific deletion of PTEN (myeloid specific PTEN-/-) display increased osteoclastogenesis in vitro and in vivo compared to wild-type mice. However, under homeostatic conditions, enhanced osteoclastogenesis did not result in systemic bone loss due to a significantly increased bone formation evidenced by an enhanced mineral apposition rate in myeloid specific PTEN-/- mice. In contrast, under inflammatory conditions in the hTNFtg mouse model of arthritis, myeloid specific PTEN-/- displayed enhanced local bone destruction as well as osteoclast formation in the inflamed joints. The extent of synovial inflammation, however, as well as recruitment of osteoclast precursor cells was not different between wt and myeloid specific PTEN-/- mice.
Conclusions These data demonstrate that enhanced PI3-Kinase activity in myeloid cells the osteoclastogenic potential of myeloid cells, leading to enhanced inflammatory local bone destruction.
Disclosure of Interest None Declared