Priority Research Paper Volume 13, Issue 24 pp 25607—25642

Figure 7. Graphical summary. 13-month-old Dmp1-PPR^KO mice showed trabecular bone loss driven by increased osteoclast number and activity and reduced osteoblast function. Mechanistically, the lack of PPR signaling in mature osteoblasts/osteocytes decreases osteoprogenitors and increases serum sclerostin, RANKL-expressing marrow adipocytes and early onset of 4-HNE+ osteocytes and p16^Ink4a upregulation in KO mice. Circulating factor(s) from these mutant mice increases, directly or indirectly, osteoclastogenic and adipogenic differentiation of BMMCs and BMSCs, respectively. Furthermore, in vitro data showed that PPR signaling induces long-lasting suppression of p21 and protects osteocytes from oxidative stress-induced intracellular ROS accumulation, cell death and senescence.