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ID 61863
Author
Mizukawa, Tomomi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nishida, Takashi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons researchmap
Akashi, Sho Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan
Kawata, Kazumi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan
Kikuchi, Sumire Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan
Kawaki, Harumi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan ORCID Kaken ID researchmap
Takigawa, Masaharu Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Kaken ID publons researchmap
Kamioka, Hiroshi Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons researchmap
Kubota, Satoshi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons researchmap
Abstract
Cellular communication network factor (CCN) family members are multifunctional matricellular proteins that manipulate and integrate extracellular signals. In our previous studies investigating the role of CCN family members in cellular metabolism, we found three members that might be under the regulation of energy metabolism. In this study, we confirmed that CCN2 and CCN3 are the only members that are tightly regulated by glycolysis in human chondrocytic cells. Interestingly, CCN3 was induced under a variety of impaired glycolytic conditions. This CCN3 induction was also observed in two breast cancer cell lines with a distinct phenotype, suggesting a basic role of CCN3 in cellular metabolism. Reporter gene assays indicated a transcriptional regulation mediated by an enhancer in the proximal promoter region. As a result of analyses in silico, we specified regulatory factor binding to the X‐box 1 (RFX1) as a candidate that mediated the transcriptional activation by impaired glycolysis. Indeed, the inhibition of glycolysis induced the expression of RFX1, and RFX1 silencing nullified the CCN3 induction by impaired glycolysis. Subsequent experiments with an anti‐CCN3 antibody indicated that CCN3 supported the survival of chondrocytes under impaired glycolysis. Consistent with these findings in vitro, abundant CCN3 production by chondrocytes in the deep zones of developing epiphysial cartilage, which are located far away from the synovial fluid, was confirmed in vivo. Our present study uncovered that RFX1 is the mediator that enables CCN3 induction upon cellular starvation, which may eventually assist chondrocytes in retaining their viability, even when there is an energy supply shortage.
Note
This is an Accepted Manuscript of an article published by Wiley
This fulltext is available in Mar 2022
Published Date
2021-03-03
Publication Title
Journal of Cellular Physiology
Publisher
Wiley
ISSN
0021-9541
NCID
AA00694856
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
File Version
author
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1002/jcp.30348
Citation
Mizukawa T, Nishida T, Akashi S, Kawata K, Kikuchi S, Kawaki H, Takigawa M, Kamioka H, Kubota S. RFX1-mediated CCN3 induction that may support chondrocyte survival under starved conditions. J Cell Physiol. 2021 Mar 3. doi: 10.1002/jcp.30348. Epub ahead of print. PMID: 33655492.
Funder Name
Japan Society for the Promotion of Science
助成番号
17K19756
17K19757
19H03817
19K22716
20K20611
20K18756