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.
Regulation of Fracture Repair and Bone Formation by ProstacyclinTechnology #2013-288
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