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Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone.
Vrahnas, Christina; Blank, Martha; Dite, Toby A; Tatarczuch, Liliana; Ansari, Niloufar; Crimeen-Irwin, Blessing; Nguyen, Huynh; Forwood, Mark R; Hu, Yifang; Ikegame, Mika; Bambery, Keith R; Petibois, Cyril; Mackie, Eleanor J; Tobin, Mark J; Smyth, Gordon K; Oakhill, Jonathan S; Martin, T John; Sims, Natalie A.
Afiliación
  • Vrahnas C; Bone Biology and Disease Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Melbourne, VIC, 3065, Australia.
  • Blank M; Department of Medicine, The University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, 3065, Australia.
  • Dite TA; MRC Protein Phosphorylation and Ubiquitylation Unit, James Black Centre, University of Dundee, Dundee, DD1 4HN, UK.
  • Tatarczuch L; Bone Biology and Disease Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Melbourne, VIC, 3065, Australia.
  • Ansari N; Department of Medicine, The University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, 3065, Australia.
  • Crimeen-Irwin B; Department of Medicine, The University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, 3065, Australia.
  • Nguyen H; Metabolic Signalling Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Melbourne, VIC, 3065, Australia.
  • Forwood MR; MRC Protein Phosphorylation and Ubiquitylation Unit, James Black Centre, University of Dundee, Dundee, DD1 4HN, UK.
  • Hu Y; Department of Veterinary Biosciences, Melbourne Veterinary School, The University of Melbourne, Parkville, VIC, 3010, Australia.
  • Ikegame M; Bone Biology and Disease Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Melbourne, VIC, 3065, Australia.
  • Bambery KR; Department of Medicine, The University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, 3065, Australia.
  • Petibois C; Bone Biology and Disease Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Melbourne, VIC, 3065, Australia.
  • Mackie EJ; School of Medical Science and Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia.
  • Tobin MJ; School of Medical Science and Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia.
  • Smyth GK; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3010, Australia.
  • Oakhill JS; Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan.
  • Martin TJ; Infrared Microspectroscopy (IRM) Beamline, ANSTO Australian Synchrotron, Clayton, VIC, 3168, Australia.
  • Sims NA; University of Bordeaux, Inserm U1029 LAMC, Allée Geoffroy Saint-Hilaire Bat. B2, 33600, Pessac, France.
Nat Commun ; 10(1): 3436, 2019 07 31.
Article en En | MEDLINE | ID: mdl-31366886
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Enfermedades del Desarrollo Óseo / Calcificación Fisiológica / Proteínas de Unión al GTP rho / Efrina-B2 Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Enfermedades del Desarrollo Óseo / Calcificación Fisiológica / Proteínas de Unión al GTP rho / Efrina-B2 Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido