Journal ArticleDOI
Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation.
Tomohiko Murakami,Atsushi Saito,Shin-ichiro Hino,Shinichi Kondo,Soshi Kanemoto,Kazuyasu Chihara,Hiroshi Sekiya,Kenji Tsumagari,Kimiko Ochiai,Kazuya Yoshinaga,Masahiro Saitoh,Riko Nishimura,Toshiyuki Yoneda,Ikuyo Kou,Tatsuya Furuichi,Shiro Ikegawa,Masahito Ikawa,Masaru Okabe,Akio Wanaka,Kazunori Imaizumi +19 more
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TLDR
The studies show that OASIS is critical for bone formation through the transcription of Col1a1 and the secretion of bone matrix proteins, and they reveal a new mechanism by which ER stress-induced signalling mediates bone formation.Abstract:
Eukaryotic cells have signalling pathways from the endoplasmic reticulum (ER) to cytosol and nuclei, to avoid excess accumulation of unfolded proteins in the ER. We previously identified a new type of ER stress transducer, OASIS, a bZIP (basic leucine zipper) transcription factor, which is a member of the CREB/ATF family and has a transmembrane domain. OASIS is processed by regulated intramembrane proteolysis (RIP) in response to ER stress, and is highly expressed in osteoblasts. OASIS(-/-) mice exhibited severe osteopenia, involving a decrease in type I collagen in the bone matrix and a decline in the activity of osteoblasts, which showed abnormally expanded rough ER, containing of a large amount of bone matrix proteins. Here we identify the gene for type 1 collagen, Col1a1, as a target of OASIS, and demonstrate that OASIS activates the transcription of Col1a1 through an unfolded protein response element (UPRE)-like sequence in the osteoblast-specific Col1a1 promoter region. Moreover, expression of OASIS in osteoblasts is induced by BMP2 (bone morphogenetic protein 2), the signalling of which is required for bone formation. Additionally, RIP of OASIS is accelerated by BMP2 signalling, which causes mild ER stress. Our studies show that OASIS is critical for bone formation through the transcription of Col1a1 and the secretion of bone matrix proteins, and they reveal a new mechanism by which ER stress-induced signalling mediates bone formation.read more
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Role of vesicular trafficking in skeletal dynamics
Gudrun Stenbeck,Fraser P. Coxon +1 more
TL;DR: New insights into the molecular control of bone remodelling raise the possibility of developing novel therapeutics for bone diseases designed to target specific aspects of this process.
Journal ArticleDOI
Regulation of endochondral ossification by transcription factors
TL;DR: A transcription factor, BBF2H7, functions as an ER stress sensor in chondrocytes through regulation of appropriate secretion of chondrogenic matrices and this work would like to discuss how the transcription factors regulate endochondral ossification.
Journal ArticleDOI
Reconstructed glycan profile for evaluation of operating status of the endoplasmic reticulum glycoprotein quality control.
Shogo Iwamoto,Shogo Iwamoto,Miho Isoyama,Makoto Hirano,Kenta Yamaya,Yukishige Ito,Ichiro Matsuo,Kiichiro Totani +7 more
TL;DR: Whether ER glycan-processing profiles in diabetic rats and osteoporotic mice as models might have different cellular status from those of normal controls is examined and glycan profiles are reconstructed, expected to be useful indexes for operational status of the ER glycoprotein quality control, and may also give information to classify some diseases.
Journal ArticleDOI
IL-12p40/IL-23p40 Blockade With Ustekinumab Decreases the Synovial Inflammatory Infiltrate Through Modulation of Multiple Signaling Pathways Including MAPK-ERK and Wnt
Renée H. Fiechter,Henriëtte M. de Jong,Leonieke J J van Mens,Inka A. Fluri,Sander W. Tas,Dominique Baeten,Nataliya Yeremenko,Marleen G H van de Sande +7 more
TL;DR: In this paper, the authors investigated the cellular and molecular pathways affected by IL-12p40/IL-23p40 blockade with ustekinumab in the synovium of PsA patients.
Journal ArticleDOI
Fat Mass and Obesity-Associated (FTO) Stimulates Osteogenic Differentiation of C3H10T1/2 Cells by Inducing Mild Endoplasmic Reticulum Stress via a Positive Feedback Loop with p-AMPK.
TL;DR: FTO induces osteogenic differentiation of C3H10T1/2 cells upon BMP2 treatment by inducing mild ER stress via a positive feedback loop with p-AMPK and activation of adenosine monophosphate-activated protein kinase (AMPK), and severe ER stress inhibits osteogenic differentiated cells by suppressing FTO expression and AMPK activation.
References
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Journal ArticleDOI
Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts
Toshihisa Komori,Hideshi Yagi,Shintaro Nomura,Akira Yamaguchi,Koichi Sasaki,Kenji Deguchi,Y Shimizu,Roderick T. Bronson,Y.-H Gao,Masahiko Inada,Makoto Sato,R Okamoto,Yukihiko Kitamura,Shusaku Yoshiki,Tadamitsu Kishimoto +14 more
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Journal ArticleDOI
The Novel Zinc Finger-Containing Transcription Factor Osterix Is Required for Osteoblast Differentiation and Bone Formation
Kazuhisa Nakashima,Xin Zhou,Gary R. Kunkel,Zhaoping Zhang,Jian Min Deng,Richard R. Behringer,Benoit de Crombrugghe +6 more
TL;DR: It is proposed that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells, because Osx null preostEoblasts express typical chondrocyte marker genes, and Osx acts downstream of Runx 2/C bfa1.
Journal ArticleDOI
Cbfa1, a Candidate Gene for Cleidocranial Dysplasia Syndrome, Is Essential for Osteoblast Differentiation and Bone Development
Florian Otto,Anders P Thornell,Tessa Crompton,Angela Denzel,Kimberly C Gilmour,Ian R Rosewell,Gordon Stamp,Rosa S.P Beddington,Stefan Mundlos,Bjorn R. Olsen,Paul B. Selby,Michael John Owen +11 more
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ER stress and the unfolded protein response.
TL;DR: A model in which the activity of UPR signaling pathways reflects the biosynthetic activity of the ER is proposed, which shows that this information is integrated into control of cellular events, which were previously not considered to be under control of ER signaling pathways.
Journal ArticleDOI
Reaching a genetic and molecular understanding of skeletal development.
Gerard Karsenty,Erwin F. Wagner +1 more
TL;DR: The role of the principal growth factors and transcription factors affecting different processes of skeletal development, chondrogenesis, joint formation, and osteogenesis are addressed and the genetic cascade leading to cell differentiation is presented.
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