Stimulation of Osteoblastic Cell Differentiation by Notch

• DOI: 10.1359/jbmr.2002.17.2.231
• Publication Date: 2006-04-27T04:16:38Z
• Authors: Ken-ICHI Tezuka; Masafumi Yasuda; Naoko Watanabe; Naoko Morimura; Kazuki Kuroda; Seiji Miyatani; Nobumichi Hozumi
• Keywords: 0301 basic medicine; Cytoplasm; Osteoblasts; Green Fluorescent Proteins; Intracellular Signaling Peptides and Proteins; Bone Morphogenetic Protein 2; Membrane Proteins; Bone Marrow Cells; Cell Differentiation; Receptors, Cell Surface; Recombinant Proteins; Luminescent Proteins; Mice; 03 medical and health sciences; Transforming Growth Factor beta; Bone Morphogenetic Proteins; Animals; Humans; Receptor, Notch2; Receptor, Notch1; Cells, Cultured; Transcription Factors

Abstract Notch is a transmembrane protein that plays critical role in the determination of cellular differentiation pathways. Although its importance development mesenchymal tissues has been suggested, skeletal not well investigated. Northern blot experiments showed expression Notch1 MC3T3-E1 osteoblastic cells at early stages. When cytoplasmic domain (Notch-IC [NIC]) delivered by an adenovirus vector was expressed cells, significant increase calcified nodule formation observed long-term cultures. Activation endogenous coculturing them with Delta-like-1 (Dll1)-expressing myeloma also resulted stimulation formation. Not only affecting formation, activation had effects on multipotent cells. Osteoblastic C3H10T1/2 induced bone morphogenetic 2 (BMP-2) significantly stimulated, whereas adipogenic suppressed strongly, resulting dominant NIC primary human marrow stem (hMSCs) both spontaneous and stimulated cell differentiation. These observations suggest regulated positively could be unique interesting target molecule for treatment osteoporosis.