Vhl deficiency in osteocytes produces high bone mass and hematopoietic defects

Gabriela G. Loots, Alexander G. Robling, Jiun C. Chang, Deepa K. Murugesh, Jamila Bajwa, Cameron Carlisle, Jennifer O. Manilay, Alice Wong, Clare E Yellowley-genetos, Damian C Genetos

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Tissue oxygen (O2) levels vary during development and disease; adaptations to decreased O2 (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.

Original languageEnglish (US)
Pages (from-to)307-314
Number of pages8
JournalBone
Volume116
DOIs
StatePublished - Nov 1 2018

Fingerprint

Osteocytes
Bone and Bones
Skeleton
Protein Isoforms
Myelopoiesis
Hematopoiesis
Gene Deletion
Homeostasis
B-Lymphocytes
Transcription Factors
Maintenance
Hypoxia
Oxygen

Keywords

  • Hematopoiesis
  • Hypoxia-inducible factor
  • Osteocyte
  • Sclerostin
  • von Hippel-Landau
  • Wnt

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Loots, G. G., Robling, A. G., Chang, J. C., Murugesh, D. K., Bajwa, J., Carlisle, C., ... Genetos, D. C. (2018). Vhl deficiency in osteocytes produces high bone mass and hematopoietic defects. Bone, 116, 307-314. https://doi.org/10.1016/j.bone.2018.08.022

Vhl deficiency in osteocytes produces high bone mass and hematopoietic defects. / Loots, Gabriela G.; Robling, Alexander G.; Chang, Jiun C.; Murugesh, Deepa K.; Bajwa, Jamila; Carlisle, Cameron; Manilay, Jennifer O.; Wong, Alice; Yellowley-genetos, Clare E; Genetos, Damian C.

In: Bone, Vol. 116, 01.11.2018, p. 307-314.

Research output: Contribution to journalArticle

Loots, GG, Robling, AG, Chang, JC, Murugesh, DK, Bajwa, J, Carlisle, C, Manilay, JO, Wong, A, Yellowley-genetos, CE & Genetos, DC 2018, 'Vhl deficiency in osteocytes produces high bone mass and hematopoietic defects', Bone, vol. 116, pp. 307-314. https://doi.org/10.1016/j.bone.2018.08.022
Loots GG, Robling AG, Chang JC, Murugesh DK, Bajwa J, Carlisle C et al. Vhl deficiency in osteocytes produces high bone mass and hematopoietic defects. Bone. 2018 Nov 1;116:307-314. https://doi.org/10.1016/j.bone.2018.08.022
Loots, Gabriela G. ; Robling, Alexander G. ; Chang, Jiun C. ; Murugesh, Deepa K. ; Bajwa, Jamila ; Carlisle, Cameron ; Manilay, Jennifer O. ; Wong, Alice ; Yellowley-genetos, Clare E ; Genetos, Damian C. / Vhl deficiency in osteocytes produces high bone mass and hematopoietic defects. In: Bone. 2018 ; Vol. 116. pp. 307-314.
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