Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders
2017
Sclerostin is a glycoprotein involved in the regulation of bone metabolism, exclusively secreted by osteocytes. It affects the activity of bone morphogenetic proteins (BMPs) and is an inhibitor of the Wnt/β-catenin metabolic pathway in bone cells. Osteocytes reduce the release of sclerostin in response to mechanical stimuli acting on bone, and thus promote the activation of osteogenic pathway Wnt/β-catenin in osteoblasts. This signaling pathway plays a key role in osteogenesis and bone turnover. Loss of sclerostin gene function is related to 3 different craniotubular hyperostosis processes: sclerosteosis, craniodiaphyseal dysplasia, and van Buchem disease. Additionally, experimental and clinical studies suggest that sclerostin may promote vascular calcification. Antibodies directed against sclerostin stimulate bone formation and represent a new therapeutic option in the treatment of diseases with increased bone resorption, such as osteoporosis and inflammatory diseases where there is generalized bone loss, periarticular osteoporosis, and cartilage damage, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and glucocorticoid-induced osteoporosis (GIO). Antibody use has the potential to offer new therapeutic approaches in the therapy of mineral and bone disorders resulting from chronic kidney disease (CKD-MBD) and vascular calcifications.
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