Functional roles of the tissue inhibitor of metalloproteinase 3 (TIMP-3) during ascorbate-induced differentiation of osteoblastic MC3T3-E1 cells

Hironao Suzuki, Yuko Nezaki, Eriko Kuno, Ikuko Sugiyama, Akifumi Mizutani, Norihiro Tsukagoshi

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1737-1743
Number of pages7
JournalBioscience, Biotechnology and Biochemistry
Volume67
Issue number8
DOIs
Publication statusPublished - Jan 1 2003

Keywords

  • Ascorbate induced osteoblastic differentiation
  • Extracellular matrix (ECM)
  • Matrix metalloproteinases (MMPs)
  • Tissue inhibitor of metalloproteinase-3 (TIMP-3)

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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