Involvement of the osteoinductive factors, Tmem119 and BMP-2, and the ER stress response PERK-eIF2α-ATF4 pathway in the commitment of myoblastic into osteoblastic cells

Calcified Tissue International
Ken-ichiro TanakaToshitsugu Sugimoto

Abstract

The osteoinductive factors BMP-2 and Tmem119 that promote the differentiation of myoblasts into osteoblasts, each increase the levels of the other. However, the relative contributions of BMP-2 and Tmem119 to the osteogenic differentiation and the mechanisms involved are incompletely understood. In the present study, we examined the relationship among BMP-2, Tmem119, and the PERK-eIF2α-ATF4 endoplasmic reticulum (ER) stress response pathway in the differentiation of C2C12 myoblasts into osteoblastic cells. Both BMP-2 and Tmem119 induced levels of the osteoblast markers Runx2, Osterix, Col1a1, ALP, and osteocalcin, as well as mineralization. BMP-2 activation of the ER stress sensor PERK stimulated phosphorylation of eIF2α and led to increased biosynthesis of the osteoblast differentiation factor ATF4. When dephosphorylation of eIF2α was blocked by the selective inhibitor salubrinal, the osteogenic effects of BMP-2 and Tmem119 were enhanced further. Although BMP-2 stimulated both P-eIF2α and ATF4 levels, Tmem119 had no effect on P-eIF2α but stimulated ATF4 only. Reduction in endogenous Tmem119 levels by siRNA reduced both basal and BMP-2-stimulated levels of the ATF4 protein. In conclusion, BMP-2 stimulates differentiation of myob...Continue Reading

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Citations

Aug 8, 2015·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Jun-ichi SatohYuko Saito
Mar 24, 2016·Cellular and Molecular Life Sciences : CMLS·Keisuke HoriuchiHideo Morioka
Aug 16, 2017·The Journal of Pharmacy and Pharmacology·Daphne P L LinCrispin R Dass
Sep 2, 2015·Antimicrobial Agents and Chemotherapy·Kahtonna C AllenKevin S Akers
Sep 30, 2017·Journal of Korean Medical Science·Duk Hwa KwonHyun Kook
Aug 25, 2019·IUBMB Life·Fataneh TavasolianAmirhossein Sahebkar
Jan 1, 2020·Intractable & Rare Diseases Research·Jun-Ichi SatohYuko Saito
Jun 16, 2016·Oncotarget·Yanzhou YangWai Yee Chan
May 13, 2017·Experimental & Molecular Medicine·Zhen-Huan JiangZhi-Jun Ge
Oct 1, 2020·Journal of Cellular and Molecular Medicine·Yun ChenYun-Zhi Feng
Jan 23, 2021·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Bao-Ming TangZhuo-Ya Wang
Mar 2, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Tianxiao HanQingsong Jiang

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