Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1
- Maxillofacial Surgery, Graduate School of Tokyo Medical and Dental University, Tokyo (Japan)
- Oral Pathology, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549 (Japan)
- Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo (Japan)
- Molecular Embryology, Graduate School of Tokyo Medical and Dental University, Tokyo (Japan)
- Laboratoire d'Oncologie Virale et Moleculaire, Universite Paris 7-D, Diderot, Paris (France)
CCN3/NOV activates the Notch signal through the carboxyl terminal cysteine-rich (CT) domain. CCN3 transfection to Kusa-A1 inhibited osteogenic differentiation and cell proliferation, which is accompanied by upregulation of Hes/Hey, Notch downstream targets, and p21, a CDK inhibitor. Upregulation of Hes/Hey and p21 was abrogated by the deletion of CT domain. Anti-proliferative activity of CCN3 was also abrogated by CT domain deletion whereas anti-osteogenic activity was not completely abrogated. We found that CT domain-deleted CCN3 still possesses antagonistic effect on BMP-2. These results suggest that CCN3 employs Notch and BMP pathways in anti-osteogenic activity while it inhibits cell proliferation uniquely by Notch/p21 pathway.
- OSTI ID:
- 21043709
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 368, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2008.02.010; PII: S0006-291X(08)00241-6; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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