Poster # 055, UC Davis Health System
Evaluation of Glucocorticoid-induced Expression of Basigin on Osteogenic Potential of Skeletal Stem Cells
Mentors: David Morales; PI: Thomas Ambrosi, MS, PhD, Dipl.Ing
Glucocorticoids (GCs) are a group of powerful, widely prescribed anti-inflammatory, immunosuppressive drugs against autoimmune diseases like rheumatoid arthritis, allergies, and asthma. But long-term use leads to bone loss and osteonecrosis, which increases the chance of fractures in patients. Glucocorticoid-induced osteoporosis (GIOP) is a significant clinical issue with limited understanding of what drives it, especially at the stem cell level. Previous research using single cell RNA sequencing (sc-RNA seq) showed Basigin/CD147 (Bsg), a transmembrane protein, to be highly expressed in skeletal stem cells (SSCs) of mice exposed to GC supplementation. Additionally, sc-RNA seq showed an increase in oxidative stress response in SSCs which may be correlated with Bsg and the pathology of osteonecrosis. To mechanistically assess elevated levels of Bsg in-vitro we lentivirally over-expressed Bsg in SSCs and generated conditioned media which was then used to treat endothelial cells. Bsg over expression led to increased levels of reactive oxygen species in endothelial cells compared to control. Furthermore, we exposed SSCs to different oxygen levels which displayed higher Bsg expression under hypoxic conditions. Interestingly, osteogenic media even under hypoxia, lowered these levels. Overall, this suggests that elevated Bsg signaling can amplify SSC and endothelial dysfunction in low oxygen, stress associated microenvironments which may be correlated with GC-induced osteonecrosis.