Betsabel Chicana1, Cristine Donham1, Alberto J Millan1, Jennifer O Manilay2,3. 1. Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA. 2. Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA. jmanilay@ucmerced.edu. 3. Department of Molecular and Cell Biology, School of Natural Sciences, University of California, 5200 North Lake Road, Merced, CA, 95343, USA. jmanilay@ucmerced.edu.
Abstract
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.
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.
Authors: Jenna N Regan; Joohyun Lim; Yu Shi; Kyu Sang Joeng; Jeffrey M Arbeit; Ralph V Shohet; Fanxin Long Journal: Proc Natl Acad Sci U S A Date: 2014-05-27 Impact factor: 11.205
Authors: Ying Wang; Chao Wan; Lianfu Deng; Ximeng Liu; Xuemei Cao; Shawn R Gilbert; Mary L Bouxsein; Marie-Claude Faugere; Robert E Guldberg; Louis C Gerstenfeld; Volker H Haase; Randall S Johnson; Ernestina Schipani; Thomas L Clemens Journal: J Clin Invest Date: 2007-06 Impact factor: 14.808
Authors: Jolly Mazumdar; W Timothy O'Brien; Randall S Johnson; Joseph C LaManna; Juan C Chavez; Peter S Klein; M Celeste Simon Journal: Nat Cell Biol Date: 2010-09-19 Impact factor: 28.824