Regulation of Fracture Repair and Bone Formation by Prostacyclin

Technology #2013-288

The balance between bone loss and deposition is important for normal bone growth and remodeling, and depends on a complex interplay between the resident bone cells: osteoclasts, osteoblasts, and osteocytes. Here we show enhanced cellular production of prostacyclin and increased intra-cellular concentrations of prostacyclin synthase in osteocytes derived from sclerostin knockout mice. Beta-catenin is increased in Sost knockout osteocytes and is associated with increased localization of the nuclear transcription factors, lymphoid-enhancer binding factor (LEF) and T-cell factor, on euchromatin. Blockade of Wnt signaling reduces cellular beta-catenin, beta-catenin and LEF nuclear localization, and reduces prostacyclin production. These observations demonstrate that sclerostin alters prostacyclin production in osteocytes via Wnt-dependent autocrine mechanisms and reveals a signaling relationship that can be exploited to enhance fracture repair and treat osteoporosis. We envisage using prostacyclin attached to hydrogels or nanparticles to increase fracture repair and bone formation.