Vhl deficiency in osteocytes produces high bone mass and hematopoietic defects

Bone
Gabriela G LootsDamian C Genetos

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.

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Citations

Feb 7, 2019·Current Osteoporosis Reports·Clare E Yellowley, Damian C Genetos
Mar 6, 2019·Current Osteoporosis Reports·Betsabel ChicanaJennifer O Manilay
Apr 16, 2019·Current Opinion in Nephrology and Hypertension·Steve Stegen, Geert Carmeliet
Jun 23, 2019·Current Osteoporosis Reports·Cristal S YeeTamara Alliston
Jan 24, 2020·Current Osteoporosis Reports·Cristine Donham, Jennifer O Manilay
Jan 29, 2021·World Journal of Stem Cells·Marta Camacho-CardenosaAntonio Casado-Díaz
Apr 5, 2021·Biochemical and Biophysical Research Communications·Jiancheng ZhengLianfu Deng
Jun 13, 2021·Current Osteoporosis Reports·Vivin Karthik, Anyonya R Guntur

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