Fig. 4

Role of ROS in bone cell fate regulation. ROS (reactive oxygen species) generation due to aging and estrogen deficiency is accompanied by increased cellular senescence characterized by the senescence-associated secretory phenotype (SASP) in the bone tissue. The SASP facilitates the accumulation of adipocytes in the bone marrow at the expense of osteoblast formation by inducing peroxisome proliferator activated receptor gamma (Pparγ) in mesenchymal progenitor cells (MSCs). Additionally, the SASP promotes myeloid progenitor development from the hematopoietic stem cell (HSC) lineage. Consequently, an elevated monocyte level is associated with an increase of osteoclast formation. Apoptotic osteocytes are involved in increased bone resorption by producing an unbalanced RANKL level. Moreover, apoptotic osteocytes induce sclerostin and Dickkopf-related protein (Dkk) 1 production, which inhibits Wnt/b-catenin mediated osteogenesis