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
Reads0
Chats0
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
Citations
More filters
Posted ContentDOI
Revealing the critical regulators of cell identity in the mouse cell atlas
TL;DR: Computational analysis of the recently published mouse cell atlas data has identified 202 gene regulatory networks whose activities are highly variable across different cell types, and predicted a small set of essential regulators for each of over 800 cell types in mouse for the first time.
Journal ArticleDOI
Master regulator for chondrogenesis, Sox9, regulates transcriptional activation of the endoplasmic reticulum stress transducer BBF2H7/CREB3L2 in chondrocytes.
Kenta Hino,Atsushi Saito,Miori Kido,Soshi Kanemoto,Rie Asada,Tomoko Takai,Min Cui,Xiang Cui,Kazunori Imaizumi +8 more
TL;DR: The present study elucidated the mechanisms of the transcriptional activation of Bbf2h7 in chondrocytes and demonstrated novel regulatory mechanisms of Sox9 for controlling the secretion of cartilage matrix proteins through the activation of BBF2H7-Sec23a signaling during chondrogenesis.
Journal ArticleDOI
Inflammation and cellular stress: a mechanistic link between immune-mediated and metabolically driven pathologies.
Eva Rath,Dirk Haller +1 more
TL;DR: The data discussed in the present review highlight the interaction of ER UPR with inflammatory pathways, metabolic processes and mitochondrial function, and their interrelation in the context of chronic diseases.
Journal ArticleDOI
Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors.
TL;DR: Current understanding of biochemical characteristics and in vivo functions of OASis family proteins, particularly focusing on OASIS and BBF2H7 are summarized.
Journal ArticleDOI
Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis
TL;DR: Understanding how UPR signaling may contribute to cartilage pathophysiology is an essential step toward therapeutic modulation of skeletal disorders that lead to osteoarthritis.
References
More filters
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.
Related Papers (5)
Signal integration in the endoplasmic reticulum unfolded protein response
David Ron,Peter Walter +1 more