Browsing by Author "Wong, Alice"

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    Vhl deficiency in osteocytes produces high bone mass and hematopoietic defects
    (Elsevier, 2018) Loots, Gabriela G.; Robling, Alexander G.; Chang, Jiun C.; Murugesh, Deepa K.; Bajwa, Jamila; Carlisle, Cameron; Manilay, Jennifer O.; Wong, Alice; Yellowley, Clare E.; Genetos, Damian C.; Anatomy and Cell Biology, School of Medicine
    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.