Functional Roles of the Tissue Inhibitor of Metalloproteinase 3 (TIMP-3) during Ascorbate-induced Differentiation of Osteoblastic MC3T3-E1 Cells
Open Access
- 1 January 2003
- journal article
- Published by Oxford University Press (OUP) in Bioscience, Biotechnology, and Biochemistry
- Vol. 67 (8) , 1737-1743
- https://doi.org/10.1271/bbb.67.1737
Abstract
The tissue inhibitor of the metalloproteinase-3 (TIMP-3) gene was isolated as a gene involved in the process of ascorbate-induced differentiation of mouse MC3T3-E1 cells by the differential display method. The functional roles of TIMP-3 were characterized by establishing stable cell lines, which constitutively expressed the TIMP-3 gene. The TIMP-3 transfectants produced type I collagen at the same level as that of normal cells in response to ascorbic acid 2-phosphate (AscP). However, the expression of the other osteoblastic marker proteins such as alkaline phosphatase (ALPase), osteopontin (OP), osteocalcin (OC), osteonectin (ON) and matrix metalloproteinases (MMPs) remained at a low level even in the presence of AscP. Furthermore, no mineralization of the extracellular matrix (ECM) occurred with the transfectants. Remodeling ECM through TIMPs and MMPs is concluded to be required for osteoblastic differentiation.Keywords
This publication has 23 references indexed in Scilit:
- How Matrix Metalloproteinases Regulate Cell BehaviorAnnual Review of Cell and Developmental Biology, 2001
- Expression of Matrix Metalloproteinases During Ascorbate-Induced Differentiation of Osteoblastic MC3T3-E1 CellsJournal of Bone and Mineral Research, 2001
- The Developmental Control of Osteoblast-Specific Gene Expression: Role of Specific Transcription Factors and the Extracellular Matrix EnvironmentCritical Reviews in Oral Biology & Medicine, 1999
- L-Ascorbic Acid 2-Phosphate Promotes Osteoblasti Differentiation of MC3T3-E1 Mediated by Accumulation of Type I Collagen.Journal of Nutritional Science and Vitaminology, 1994
- Tumor Cell Interactions with the Extracellular Matrix During Invasion and MetastasisAnnual Review of Cell Biology, 1993
- Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimizationNucleic Acids Research, 1993
- Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cellsJournal of Bone and Mineral Research, 1992
- In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria.The Journal of cell biology, 1983
- Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes.Proceedings of the National Academy of Sciences, 1977
- RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexaminationBiochemistry, 1977