Interaction of Tmem119 and the bone morphogenetic protein pathway in the commitment of myoblastic into osteoblastic cells

Bone
Ken-ichiro TanakaH Kaji

Abstract

Bone morphogenetic proteins (BMPs) are critical for bone regeneration and induce ectopic bone formation in vivo. The constitutively activating mutation (R206H) of the BMP type 1 receptor, activin A type 1 receptor/activin-like kinase 2 (ACVR1/ALK2), underlies the molecular pathogenesis of fibrodysplasia ossificans progressiva (FOP) in which heterotopic ossification occurs in muscle tissue. In the present study, we performed a comparative DNA microarray analysis between stable empty vector- and ALK2(R206H)-transfected mouse myoblastic C2C12 cells. Forty genes were identified whose expression was increased >3.5 times in the experimental group versus the control. The bone formation-related factor, Tmem119, was included in this group. Osteoblast differentiation markers and mineralization were enhanced in C2C12 cells stably expressing Tmem119. Differentiation of myoblastic cells into myotubes was suppressed but differentiation into chondrocytes was little affected. Transcriptional activity of the BMP-2 signaling molecules, Smad1/5, was increased even in the absence of exogenous BMP-2. Endogenous BMP-2 levels positively correlated with Tmem119 levels. A BMP-2/4 neutralizing antibody and dorsomorphin, an ALK2 inhibitor, antagonized Tm...Continue Reading

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Citations

Mar 14, 2013·Current Opinion in Clinical Nutrition and Metabolic Care·Hiroshi Kaji
Apr 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Umit A KayisliCharles J Lockwood
Feb 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Mariko L BennettBen A Barres
Jun 14, 2014·Biochemical and Biophysical Research Communications·Ken-ichiro TanakaToshitsugu Sugimoto
Mar 26, 2015·Ageing Research Reviews·Camille TagliaferriVéronique Coxam
Aug 28, 2014·Annals of Anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft·Christiane Kunert-KeilTomasz Gredes
Apr 8, 2014·Journal of Bone Metabolism·Hiroshi Kaji
Dec 19, 2014·Journal of Cellular Biochemistry·Naoyuki Kawao, Hiroshi Kaji
Nov 23, 2013·Journal of Cellular Physiology·Gregory R SondagFayez F Safadi
Sep 26, 2019·Biochemical Society Transactions·Caroline Busch, Helen Wheadon
May 13, 2017·Experimental & Molecular Medicine·Zhen-Huan JiangZhi-Jun Ge
Aug 15, 2021·Neuron·Anaelle Aurelie DumasMarco Prinz
Sep 23, 2021·Biological Reviews of the Cambridge Philosophical Society·Marcus Augusto-OliveiraAlexei Verkhratsky

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