Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1.
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.
Katsuki
Yuko
Y
Maxillofacial Surgery, Graduate School of Tokyo Medical and Dental University, Tokyo, Japan.
Sakamoto
Kei
K
Minamizato
Tokutaro
T
Makino
Hatsune
H
Umezawa
Akihiro
A
Ikeda
Masa-Aki
MA
Perbal
Bernard
B
Amagasa
Teruo
T
Yamaguchi
Akira
A
Katsube
Ken-Ichi
K
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D055514:Nephroblastoma Overexpressed Protein; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
C526317:CCN2 protein, human; C526319:CCN3 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D055513:Connective Tissue Growth Factor