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Title: Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1

Journal Article · · Biochemical and Biophysical Research Communications
 [1]; ;  [2]; ;  [3];  [4];  [5];  [1];  [2];  [2]
  1. Maxillofacial Surgery, Graduate School of Tokyo Medical and Dental University, Tokyo (Japan)
  2. Oral Pathology, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549 (Japan)
  3. Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo (Japan)
  4. Molecular Embryology, Graduate School of Tokyo Medical and Dental University, Tokyo (Japan)
  5. 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