Master regulator for chondrogenesis, sox9, regulates transcriptional activation of the endoplasmic reticulum stress transducer BBF2H7/CREB3L2 in chondrocytes
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The endoplasmic reticulum (ER) stress transducer, box B-binding factor 2 human homolog on chromosome 7 (BBF2H7), is a basic leucine zipper (bZIP) transmembrane transcription factor. This molecule is activated in response to ER stress during chondrogenesis. The activated BBF2H7 accelerates cartilage matrix protein secretion through the up-regulation of Sec23a, which is responsible for protein transport from the ER to the Golgi apparatus and is a target of BBF2H7. In the present study, we elucidated the mechanisms of the transcriptional activation of Bbf2h7 in chondrocytes. The transcription of Bbf2h7 is regulated by Sex determining region Y-related high-mobility group box 9 (Sox9), a critical factor for chondrocyte differentiation that facilitates the expression of one of the major cartilage matrix proteins Type II collagen (Col2), through binding to the Sox DNA-binding motif in the Bbf2h7 promoter. BBF2H7 is activated as a transcription factor in response to physiological ER stress caused by abundant synthesis of cartilage matrix proteins, and consequently regulates the secretion of cartilage matrix proteins. Taken together, our findings demonstrate novel regulatory mechanisms of Sox9 for controlling the secretion of cartilage matrix proteins through the activation of BBF2H7-Sec23a signaling during chondrogenesis.
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SOX9 acts as a master regulator.
“highlighting the role of SOX9 as a master regulator (17,54,55).”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [55]
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- Authors
- Hino, K., Saito, A., Kido, M., Kanemoto, S., Asada, R., Takai, T., Cui, M., Cui, X., & Imaizumi, K.
- Affiliations
- Hiroshima University (JP)
- Corresponding author
- Saito, Atsushi
- Imaizumi, Kazunori
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 289
- Issue
- 20
- Pages
- 13810-13820
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4022855
- OpenAlex
- W1981144776
- Cited by
- 84
- References
- 49
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 3 · 2020: 11 · 2019: 10 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 7 · 2014: 2
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (25650069, 25251014, 13J00677, 24689058, 24659678)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- SOX9, CREB3L2, chondrogenesis, chondrocytes, endoplasmic reticulum stress, transcriptional activation, SEC23A, type II collagen, bZIP transcription factors, cartilage matrix
- MeSH terms
- Animals, Humans, Signal Transduction, Transcriptional Activation, Up-Regulation, Chondrocytes, Chondrogenesis, Cell Proliferation, Basic-Leucine Zipper Transcription Factors, Rats, SOX9 Transcription Factor, Endoplasmic Reticulum Stress, Matrilin Proteins
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