Cited by 84Endoplasmic Reticulum Stress and DiseaseOsteoarthritis Treatment and MechanismsIon Channels and Receptors

Master regulator for chondrogenesis, sox9, regulates transcriptional activation of the endoplasmic reticulum stress transducer BBF2H7/CREB3L2 in chondrocytes

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Hino, Kenta, Saito, Atsushi, Kido, Miori, Kanemoto, Soshi, Asada, Rie, Takai, Tomoko, Cui, Min, Cui, Xiang +1 more·2014·Journal of Biological Chemistry

Abstract

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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  1. [28]Zhao Q. Eberspaecher H. Lefebvre V. De Crombrugghe B. (1997) Parallel expression of Sox9 and Col2a1 in cells undergoing chondrogenesis. Dev. Dyn. 209, 377– 386 9264261

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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)
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
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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