Medicine (St Vincent's) - Research Publications

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Author: Crimeen-Irwin, Blessing × Author: Martin, Thomas × End date: 2019 × Start date: 2018 ×

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    Autocrine and Paracrine Regulation of the Murine Skeleton by Osteocyte-Derived Parathyroid Hormone-Related Protein
    Ansari, N ; Ho, PWM ; Crimeen-Irwin, B ; Poulton, IJ ; Brunt, AR ; Forwood, MR ; Pajevic, PD ; Gooi, JH ; Martin, TJ ; Sims, NA (WILEY, 2018-01)
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    Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone (vol 10, 3436, 2019)
    Vrahnas, C ; Blank, M ; Dite, TA ; Tatarczuch, L ; Ansari, N ; Crimeen-Irwin, B ; Huynh, N ; Forwood, MR ; Hu, Y ; Ikegame, M ; Bambery, KR ; Petibois, C ; Mackie, EJ ; Tobin, MJ ; Smyth, GK ; Oakhill, JS ; Martin, TJ ; Sims, NA (NATURE PUBLISHING GROUP, 2019-11-04)
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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    Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone
    Vrahnas, C ; Blank, M ; Dite, TA ; Tatarczuch, L ; Ansari, N ; Crimeen-Irwinl, B ; Huynh, N ; Forwood, MR ; Hu, Y ; Ikegame, M ; Bambery, KR ; Petibois, C ; Mackie, EJ ; Tobin, MJ ; Smyth, GK ; Oakhill, JS ; Martin, TJ ; Sims, NA (Nature Research (part of Springer Nature), 2019-07-31)
    Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass.