Absence of E2f1 Negates Pro-osteogenic Impacts of p21 Absence

In this study we aimed to investigate the interplay betweenp21 andE2f1 and determine if the pro-regenerative osteogenic effects observed with the loss ofp21 areE2f1 dependent. To accomplish this, we employed knockoutp21 andE2f1 mice and additionally generated ap21/E2f1 double knockout. These mice underwent burr-hole injuries to their proximal tibiae and healing was assessed over 7  days via microCT imaging. We found thatp21 andE2f1 play distinct roles in bone regeneration where the loss ofp21 increased trabecular bone formation and loss ofE2f1 increased cortical bone formation, yet loss ofE2f1 led to poorer bone repair overall. Furthermore, whenE2f1 was absent, either individually or simultaneously withp21, there was a dramatic decrease of the number of osteoblasts, osteoclasts, and chondrocytes at the site of injury compared top21−/− andC57BL/6 mice. Together, these results suggest thatE2f1 regulates the cell populations required for bone repair and has a distinct role in bone formation/repair compared top21−/−E2f1−/−. These results highlight the possibility of cell cycle and/orp21/E2f1 being potential druggable targets that could be leveraged in clinical therapies to improve bone healing in pathologies such as osteoporosis.
Source: Calcified Tissue International - Category: Orthopaedics Source Type: research