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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Book ChapterDOI
New Target Sites for Treatment of Osteoporosis.
TL;DR: This chapter summarizes recent developments in the search and development of novel anti-osteoporotic agents, with a particular focus on therapeutic approaches based on the potential application of inorganic polymers and combinations.
Dissertation
Investigations of the Ufm1 pathway and its association with a familial form of hip dysplasia
TL;DR: Higher expression of Ufsp2 in bone and secondary ossification centres as well as upregulation of components of the Ufm1 system in response to ER stress suggests that the molecular pathway between the UFSP2 mutation and the BHD phenotype may relate to abnormal ER stress responses during osteoblast differentiation.
Journal ArticleDOI
Cartilage -specific knockout of Sirt1 significantly reduces bone quality and catch-up growth efficiency.
Biana Shtaif,Meytal Bar-Maisels,Yankel Gabet,Sahar Hiram-Bab,Michal Yackobovitch-Gavan,Moshe Phillip,Moshe Phillip,Galia Gat-Yablonski,Galia Gat-Yablonski +8 more
TL;DR: Results suggest that SIRT1 may serve as a novel therapeutic target for short stature by modulating the response of the epiphyseal growth plate (EGP) to nutritional manipulation.
Journal ArticleDOI
Calcium-Collagen Coupling is Vital for Biomineralization Schedule.
TL;DR: In this article, a novel interplay between calcium concentration and collagen production is observed, and it is shown that osteoblasts can independently and directly regulate the process of biomineralization via this coupling.
Journal ArticleDOI
Protease Sets Site-1 on Lysosomes
TL;DR: The authors show that the protease cleaves a precursor form of N-acetylglucosamine (GlcNAc)-1-phosphotransferase, an enzyme that catalyzes an essential step in forming the mannose 6-ph phosphate signal that targets many enzymes to lysosomes.
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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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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