Master regulator for chondrogenesis, Sox9, regulates transcriptional activation of the endoplasmic reticulum stress transducer BBF2H7/CREB3L2 in chondrocytes.
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.
From the Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Kenta
K
Hino
From the Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan asaito@hiroshima-u.ac.jp.
Atsushi
A
Saito
From the Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Miori
M
Kido
From the Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Soshi
S
Kanemoto
From the Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Rie
R
Asada
From the Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Tomoko
T
Takai
From the Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Min
M
Cui
From the Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Xiang
X
Cui
From the Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan imaizumi@hiroshima-u.ac.jp.
Kazunori
K
Imaizumi
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D020219:Chondrogenesis; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D064235:Matrilin Proteins / Q000378:metabolism; D051381:Rats; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D015854:Up-Regulation
D050976:Basic-Leucine Zipper Transcription Factors; C544811:Creb3l2 protein, mouse; D064235:Matrilin Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse
BBF2H7; Cartilage; Cell Biology; Chondrogenesis; ER Stress Transducer; Protein Secretion; Sox9; Transcription Factors