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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Journal ArticleDOI
Unfolded protein response‐mediated modulation of mesenchymal stem cells
Fataneh Tavasolian,Fataneh Tavasolian,Ahmad Zavaran Hosseini,Ali Mirzaei,Elham Abdollahi,Elham Abdollahi,Pouria Jandaghi,Sara Soudi,Mahmood Naderi,Ehsan Saburi,Amir Abbas Momtazi-Borojeni,Thomas P. Johnston,Amirhossein Sahebkar +12 more
TL;DR: The present review aimed to explore and discuss the effects of the UPR pathways on mesenchymal stem cells, which can be both cytoprotective and/or cytotoxic depending on the duration of UPR activation and the type of host cell.
Journal ArticleDOI
Regulation of cAMP Responsive Element Binding Protein 3-Like 1 (Creb3l1) Expression by Orphan Nuclear Receptor Nr4a1.
TL;DR: It is shown that increasing Creb3l1 transcription by raising cAMP levels in mouse pituitary AtT20 cells automatically initiates cleavage of Creb 3l1, leading to a greater abundance of the transcriptionally active N-terminal portion.
Book ChapterDOI
Heritable Skeletal Disorders Arising from Defects in Processing and Transport of Type I Procollagen from the ER: Perspectives on Possible Therapeutic Approaches.
TL;DR: A perspective on possible therapeutic interventions for associated heritable craniofacial and skeletal disorders is provided, considering different orders of complexity, from the cellular level by manipulation of proteostasis pathways to higher levels involving cell-based therapies for bone repair and regeneration.
Journal ArticleDOI
Chemotherapy Controls Metastasis Through Stimulatory Effects on GRP78 and Its Transcription Factor CREB3L1.
Annat Raiter,Julia Lipovetsky,Lucila Hyman,Shany Mugami,Tali Ben-Zur,Rinat Yerushalmi,Rinat Yerushalmi +6 more
TL;DR: Findings elucidate a potential pathway to the development of a novel treatment strategy for metastatic TNBC based on modulating CREB3L1 and cell-surface GRP78 expression by chemotherapy andGRP78-targeted drugs.
Dissertation
The role of endoplasmic reticulum stress in vascular calcification
TL;DR: It is suggested that ER stress can induce changes that lead to osteogenic differentiation and calcification of VSMCs, a regulated process mediated by vascular smooth muscle cells with similarities to developmental osteogenesis.
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
TL;DR: The data suggest that both intramembranous and endochondral ossification were completely blocked, owing to the maturational arrest of osteoblasts in the mutant mice, and demonstrate that Cbfa1 plays an essential role in osteogenesis.
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
TL;DR: The Cbfa1 gene is essential for osteoblast differentiation and bone formation, and the C bfa1 heterozygous mouse is a paradigm for a human skeletal disorder.
Journal ArticleDOI
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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