Regulation of chondrocytic phenotype by micro RNA 18a: Involvement of Ccn2/Ctgf as a major target gene

Ohgawara, Toshihiro; Kubota, Satoshi; Kawaki, Harumi; Kondo, Seiji; Eguchi, Takanori; Kurio, Naito; Aoyama, Eriko; Sasaki, Akira; Takigawa, Masaharu

doi:10.1016/j.febslet.2009.02.025

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Volume 583, Issue 6 , Pages 1006-1010, 18 March 2009

Regulation of chondrocytic phenotype by micro RNA 18a: Involvement of Ccn2/Ctgf as a major target gene

Edited by Zhijie Chang

Toshihiro Ohgawara
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho Okayama, 700-8525, Japan
- Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Satoshi Kubota
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho Okayama, 700-8525, Japan
- Corresponding authors. Address: Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan. Fax: +81 86 235 6649.
Harumi Kawaki
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho Okayama, 700-8525, Japan
Seiji Kondo
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho Okayama, 700-8525, Japan
Takanori Eguchi
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho Okayama, 700-8525, Japan
Naito Kurio
- Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Eriko Aoyama
- Biodental Research Center, Okayama University Dental School, Okayama, Japan
Akira Sasaki
- Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Masaharu Takigawa
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho Okayama, 700-8525, Japan
- Biodental Research Center, Okayama University Dental School, Okayama, Japan
- Corresponding authors. Address: Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan. Fax: +81 86 235 6649.

Received 28 November 2008; received in revised form 12 February 2009; accepted 15 February 2009. published online 23 February 2009.

Abstract

We searched for miRNAs that were down-regulated in chondrocytic cells and predicted to target CCN2/connective tissue growth factor (CCN2/CTGF) that promotes endochondral ossification. Among them, expression of miR-18a was most strongly repressed in chondrocytic cells. Reporter gene analysis confirmed the functionality of an miR-18a target in the 3′-untranslated region of Ccn2 mRNA, which was predicted in silico. Indeed, introduction of miR-18a efficiently repressed the CCN2 production from chondrocytic cells. Finally, transfected miR-18a significantly repressed the mature chondrocytic phenotype. Our present study revealed a regulatory role for miR-18a in chondrocytic differentiation through CCN2.

Keywords: Connective tissue growth factor, CCN family, Micro RNA, miR-18a, Chondrocyte