Seth Krebs, “p21 Inhibition Improves Bone Regeneration”
Mentor: Priyatha Premnath, Biomedical Engineering
A common gene found in both humans and mice is p21, a cell cycle regulator. Previous studies have demonstrated a role for p21 in limb regeneration in mice. Similarly, our lab has shown that loss of p21 can increase bone formation after an injury in mice. Mesenchymal stem cells (MSCs) were found to be one of the reasons for improved bone properties. The experimental drug UC2288 is a known p21 inhibitor. Commonly used in anti-cancer therapies, it can be used to specifically target MSCs and inhibit p21. MSCs are multipotent, meaning they turn into several different cell types such as bone, cartilage, fat, and muscle. We are testing the efficacy of UC2288 in improving osteogenic capacity, i.e., the capacity of MSCs to turn into osteoblasts rather than cartilage or fat cells. By increasing the bone forming capacity of MSCs, we will be able to increase bone formation. These results will help us create translational therapies in bone healing and regeneration, especially for pathologies like osteoporosis or fractures that occur in aged patients where bone healing pathways are compromised.