Wnt Antagonists in Hematopoietic and Immune Cell Fate: Implications for Osteoporosis Therapies

AbstractPurpose of ReviewWe reviewed the current literature on the roles of the Wnt antagonists sclerostin (Sost) and sclerostin-containing domain protein 1 (Sostdc1) on bone homeostasis, the relationship of the hypoxia-inducible factor (Hif) and von Hippel-Lindau (Vhl) pathways on Sost expression, and how changes in bone induced by depletion ofSost, Sostdc1, andVhl affect hematopoietic cells.Recent FindingsB cell development is adversely affected in Sost-knockout mice and is more severely affected inVhl-knockout mice. Inflammation in theSost−/− bone microenvironment could alter hematopoietic stem cell behavior.Sostdc1−/− mice display defects in natural killer cell development and cytotoxicity.SummaryDepletion of Sost and Sostdc1 have effects on immune cell function that warrant investigation in patients receiving Wnt antagonist-depleting therapies for treatment of bone diseases. Additional clinical applications for manipulation of Wnt antagonists include cancer immunotherapies, stem cell transplantation, and directed differentiation to immune lineages.

Source: Current Osteoporosis Reports - March 4, 2019 Category: Orthopaedics Source Type: research