| RRC ID |
41493
|
| 著者 |
Tezuka K, Yasuda M, Watanabe N, Morimura N, Kuroda K, Miyatani S, Hozumi N.
|
| タイトル |
Stimulation of osteoblastic cell differentiation by Notch.
|
| ジャーナル |
J Bone Miner Res
|
| Abstract |
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.
|
| 巻・号 |
17(2)
|
| ページ |
231-9
|
| 公開日 |
2002-2-1
|
| DOI |
10.1359/jbmr.2002.17.2.231
|
| PMID |
11811553
|
| MeSH |
Animals
Bone Marrow Cells / cytology
Bone Marrow Cells / drug effects
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins / pharmacology
Cell Differentiation*
Cells, Cultured
Cytoplasm
Green Fluorescent Proteins
Humans
Intracellular Signaling Peptides and Proteins
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mice
Osteoblasts / cytology*
Osteoblasts / drug effects
Osteoblasts / metabolism*
Receptor, Notch1
Receptor, Notch2
Receptors, Cell Surface
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Transcription Factors*
Transforming Growth Factor beta*
|
| IF |
5.854
|
| 引用数 |
145
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126)
10T1/2(RCB0247) |
