• myGriffith
    • Staff portal
    • Contact Us⌄
      • Future student enquiries 1800 677 728
      • Current student enquiries 1800 154 055
      • International enquiries +61 7 3735 6425
      • General enquiries 07 3735 7111
      • Online enquiries
      • Staff phonebook
    View Item 
    •   Home
    • Griffith Research Online
    • Conference outputs
    • View Item
    • Home
    • Griffith Research Online
    • Conference outputs
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

  • All of Griffith Research Online
    • Communities & Collections
    • Authors
    • By Issue Date
    • Titles
  • This Collection
    • Authors
    • By Issue Date
    • Titles
  • Statistics

  • Most Popular Items
  • Statistics by Country
  • Most Popular Authors
  • Support

  • Contact us
  • FAQs
  • Admin login

  • Login
  • Bone strength and mineralization are regulated independently of bone mass by ephrinB2-dependent autophagic processes in osteocytes

    Author(s)
    Christina, Vrahnas
    Dite, Toby
    Hu, Yifang
    Huynh, Nguyen
    Forwood, Mark R
    Bambery, Keith R
    Tobin, Mark J
    Smyth, Gordon K
    Martin, T John
    Sims, Natalie A
    Griffith University Author(s)
    Forwood, Mark R.
    Nguyen, Huynh
    Year published
    2018
    Metadata
    Show full item record
    Abstract
    Bone formation has two phases: a rapid initiation (primary mineralization), followed by slower accrual of mineral (secondary mineralization) that continues until that portion of bone is renewed by remodeling. Initiation of bone mineralization, and late stage osteoblast differentiation, requires expression of EphrinB2 (Efnb2) in the osteoblast lineage, but the function of EphrinB2 in matrix-embedded osteocytes is not known.We previously reported at this meeting that osteocyte-specific EphrinB2 null mice (Dmp1Cre.Efnb2f/f) exhibit an intrinsic defect in material strength. Their brittle bone phenotype was not associated with ...
    View more >
    Bone formation has two phases: a rapid initiation (primary mineralization), followed by slower accrual of mineral (secondary mineralization) that continues until that portion of bone is renewed by remodeling. Initiation of bone mineralization, and late stage osteoblast differentiation, requires expression of EphrinB2 (Efnb2) in the osteoblast lineage, but the function of EphrinB2 in matrix-embedded osteocytes is not known.We previously reported at this meeting that osteocyte-specific EphrinB2 null mice (Dmp1Cre.Efnb2f/f) exhibit an intrinsic defect in material strength. Their brittle bone phenotype was not associated with any change in moment of inertia, osteoblast numbers, nor any defect in the initiation of osteoid mineralization. However, secondary mineralization was significantly accelerated: after initiation of mineralization, mineral:matrix ratio, and carbonate:matrix ratio increased more rapidly in EphrinB2-deficient bones than controls (detected by synchrotron-based Fourier-transform infrared microspectroscopy). This indicated that osteocytic ephrinB2 suppresses mineral accumulation in bone.To identify novel mechanisms by which osteocytes regulate secondary mineralization bone mass, we carried out RNA sequencing of marrow-flushed cortical bone from Dmp1Cre.Efnb2f/f brittle-bone mice and Dmp1Cre control littermates. This revealed 782 significantly up-regulated genes and 1024 down-regulated genes (FDR < 0.05). Genes previously known to regulate mineralization (e.g. Dmp1, Mepe, Sost, Phospho1, Enpp1, Enpp2) were not significantly modified by EphrinB2 deletion, and no regulation of the collagen type I genes (Col1a1 or Col1a2) was detected. By a literature search, we identified that >30% of the top 30 differentially expressed genes are associated with autophagy, a mechanism that mediates intracellular recycling and exocytic secretion. We therefore generated stable ephrinB2-deficient osteocyte cell lines (Ocy454) using shRNA. EphrinB2-deficient osteocytes deposited greater amounts of mineral in vitro than controls. They also showed a significantly greater increase in autophagic flux than control cells (the increase in LC3-II:I ratio in response to chloroquine treatment was increased by 30% compared to controls). This suggests that secondary mineralization of the bone matrix is controlled by autophagic processes in osteocytes, in a manner that is limited by ephrinB2. Such processes may be disrupted in conditions of bone fragility that are independent of bone mass.
    View less >
    Conference Title
    Journal of Bone and Mineral Research
    Volume
    33
    Issue
    S1
    Publisher URI
    https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.3621
    Subject
    Biological Sciences
    Engineering
    Medical and Health Sciences
    Science & Technology
    Life Sciences & Biomedicine
    Endocrinology & Metabolism
    Publication URI
    http://hdl.handle.net/10072/402625
    Collection
    • Conference outputs

    Footer

    Disclaimer

    • Privacy policy
    • Copyright matters
    • CRICOS Provider - 00233E

    Tagline

    • Gold Coast
    • Logan
    • Brisbane - Queensland, Australia
    First Peoples of Australia
    • Aboriginal
    • Torres Strait Islander