Figure 3. FoxOs decrease osteoclast numbers and bone resorption.

FoxOs play an essential role in the response to physiologic oxidative stress and thereby promote survival and self-renewal of hematopoietic stem cells. In contrast, activation of FoxO in osteoclast precursor cells attenuates resorption and increases bone mass. In line with a cell autonomous inhibitory action of FoxOs on osteoclast generation and/or survival, Akt and Mst1 kinase activity promote and attenuate osteoclast number, respectively. However, it is unknown whether the actions Akt and Mst1 in osteoclastic cells are mediated by FoxOs. FoxO activity in osteoblast also decreases osteoclast number via increased Opg expression or other mechanisms.