Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone
Christina Vrahnas, Martha Blank, Toby A Dite, Liliana Tatarczuch, Niloufar Ansari, Blessing Crimeen-Irwinl, Nguyen Huynh, Mark R Forwood, Yifang Hu, Mika Ikegame, Keith R Bambery, Cyril Petibois, Eleanor J Mackie, Mark J Tobin, Gordon K Smyth, Jonathan S Oakhill, T John Martin, Natalie A Sims
Nature Communications | Nature Research (part of Springer Nature) | Published : 2019
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 accum..View full abstract
Awarded by NHMRC
We thank the staff of the St. Vincent's Health Bioresources Center for excellent animal care and assistance, Mr Joshua Johnson and Mrs Ingrid Poulton for technical assistance with histology, Dr. Roger Curtain (Bio21) for technical assistance with BSEM, Dr. Paul Roschger for advice on BSEM analysis, Dr. Eleftherios Paschalis for advice on collagen crosslinking analysis, and Dr. Elizabeth Allan for work on the Kusa 4b10 cells. This work was supported by NHMRC Grants 1042129 and 1081242 to N.A.S. and T.J.M., Program Grant 1054618 to G.K.S., and a Brockhoff Foundation Grant to C.V. J.S.O. was supported by an ARC Future Fellowship. N.A.S. was supported by an NHMRC Senior Research Fellowship and by the SVI Brenda Shanahan Fellowship. Part of this work was untaken at the Infrared Microspectroscopy Beamline at the Australian Synchrotron, part of ANSTO. C.V. also thanks the Australia and New Zealand Bone and Mineral Society for the award of the Christine & T.J. Martin Travel Award, which allowed the laboratory visit to C.P. St. Vincent's Institute acknowledges the support of the Victorian State Government OIS program.