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

Autor: Chicana B; Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA., Donham C; Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA., Millan AJ; Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA., Manilay JO; Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA. jmanilay@ucmerced.edu.; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, 5200 North Lake Road, Merced, CA, 95343, USA. jmanilay@ucmerced.edu.
Jazyk: angličtina
Zdroj: Current osteoporosis reports [Curr Osteoporos Rep] 2019 Apr; Vol. 17 (2), pp. 49-58.
DOI: 10.1007/s11914-019-00503-3
Abstrakt: Purpose of Review: We 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 of Sost, Sostdc1, and Vhl affect hematopoietic cells.
Recent Findings: B cell development is adversely affected in Sost-knockout mice and is more severely affected in Vhl-knockout mice. Inflammation in the Sost -/- bone microenvironment could alter hematopoietic stem cell behavior. Sostdc1 -/- mice display defects in natural killer cell development and cytotoxicity. Depletion 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.
Databáze: MEDLINE
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