Vhl deficiency in osteocytes produces high bone mass and hematopoietic defects.

Autor: Loots GG; Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA, USA; Molecular Cell Biology Unit, School of Natural Sciences, UC Merced, Merced, CA, USA., Robling AG; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA., Chang JC; Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA, USA; Molecular Cell Biology Unit, School of Natural Sciences, UC Merced, Merced, CA, USA., Murugesh DK; Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA, USA., Bajwa J; Molecular Cell Biology Unit, School of Natural Sciences, UC Merced, Merced, CA, USA., Carlisle C; Molecular Cell Biology Unit, School of Natural Sciences, UC Merced, Merced, CA, USA., Manilay JO; Molecular Cell Biology Unit, School of Natural Sciences, UC Merced, Merced, CA, USA., Wong A; Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA, USA., Yellowley CE; Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA, USA., Genetos DC; Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA, USA. Electronic address: dgenetos@ucdavis.edu.
Jazyk: angličtina
Zdroj: Bone [Bone] 2018 Nov; Vol. 116, pp. 307-314. Date of Electronic Publication: 2018 Aug 30.
DOI: 10.1016/j.bone.2018.08.022
Abstrakt: Tissue oxygen (O 2 ) levels vary during development and disease; adaptations to decreased O 2 (hypoxia) are mediated by hypoxia-inducible factor (HIF) transcription factors. HIFs are active in the skeleton, and stabilizing HIF-α isoforms cause high bone mass (HBM) phenotypes. A fundamental limitation of previous studies examining the obligate role for HIF-α isoforms in the skeleton involves the persistence of gene deletion as osteolineage cells differentiate into osteocytes. Because osteocytes orchestrate skeletal development and homeostasis, we evaluated the influence of Vhl or Hif1a disruption in osteocytes. Osteocytic Vhl deletion caused HBM phenotype, but Hif1a was dispensable in osteocytes. Vhl cKO mice revealed enhanced canonical Wnt signaling. B cell development was reduced while myelopoiesis increased in osteocytic Vhl cKO, revealing a novel influence of Vhl/HIF-α function in osteocytes on maintenance of bone microarchitecture via canonical Wnt signaling and effects on hematopoiesis.
(Copyright © 2018. Published by Elsevier Inc.)
Databáze: MEDLINE
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