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Stimulation of Osteoblastic Cell Differentiation by Notch
Author(s) -
Tezuka KenICHI,
Yasuda Masafumi,
Watanabe Naoko,
Morimura Naoko,
Kuroda Kazuki,
Miyatani Seiji,
Hozumi Nobumichi
Publication year - 2002
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2002.17.2.231
Subject(s) - notch signaling pathway , microbiology and biotechnology , mesenchymal stem cell , adipogenesis , cellular differentiation , bone morphogenetic protein , chemistry , stromal cell , bone morphogenetic protein 2 , osteoblast , biology , signal transduction , cancer research , in vitro , biochemistry , gene
Notch is a transmembrane protein that plays a critical role in the determination of cellular differentiation pathways. Although its importance in the development of mesenchymal tissues has been suggested, its role in skeletal tissues has not been well investigated. Northern blot experiments showed the expression of Notch1 in MC3T3‐E1 osteoblastic cells at early differentiation stages. When a Notch1 cytoplasmic domain (Notch‐IC [NIC]) delivered by an adenovirus vector was expressed in osteoblastic MC3T3‐E1 cells, a significant increase in calcified nodule formation was observed in long‐term cultures. Activation of endogenous Notch in MC3T3‐E1 by coculturing them with Delta‐like‐1 (Dll1)‐expressing myeloma cells also resulted in a stimulation of calcified nodule formation. Not only affecting nodule formation, Notch activation also had effects on osteoblastic differentiation of multipotent mesenchymal cells. Osteoblastic differentiation of C3H10T1/2 cells induced by bone morphogenetic protein 2 (BMP‐2) was significantly stimulated, whereas adipogenic differentiation was suppressed strongly, resulting in a dominant differentiation of osteoblastic cells. NIC expression in primary human bone marrow mesenchymal stem cells (hMSCs) also induced both spontaneous and stimulated osteoblastic cell differentiation. These observations suggest that osteoblastic cell differentiation is regulated positively by Notch and that Notch could be a unique and interesting target molecule for the treatment of osteoporosis.