Poster #048
Investigating Sclerostin Antibody Effects on Osteochondral Progenitors
Mentor: Dr. Alessia Morato, Ph.D.; PI: Dr. Gabriela Loots, Ph.D.
The pharmacologic inhibition of Sclerostin (Sost) via targeting antibodies (Scl-Ab) is an effective anabolic treatment against bone-loss-related disorders, but the mechanisms remain unclear. We hypothesize that Scl-Ab enhances bone formation by promoting the differentiation of osteoprogenitor cells (OCPs) into osteoblasts (OBs) and osteocytes (OCYs). SostiCOIN/iCOIN; Col2a1-CreERT2 mice received five daily intraperitoneal tamoxifen (TMX; 75mg/Kg) injections to delete Sost in OCPs, and bone mineral density (BMD) was quantified weekly by dual-energy X-ray absorptiometry (DEXA). Reporter mice Col2a1-CreERT2; Ai9; Col1a-GFP, labeling OCPs red and OB/OCY green, received five daily TMX injections, followed by two subcutaneous Scl-Ab injections (25mg/Kg). Lumbar spines and femurs were harvested for histology to assess OCP differentiation into OB. Preliminary results indicate OCP-specific Sost deletion elicits a high bone mass phenotype, and pharmacologic Sost inhibition triggers OCP expansion, likely leading to OB differentiation. These experiments highlight the mechanism by which Sost inactivation promotes de novo bone formation.