Functional Roles of the Tissue Inhibitor of Metalloproteinase 3 (TIMP-3) during Ascorbate-induced Differentiation of Osteoblastic MC3T3-E1 Cells | Zendy

Hironao Suzuki | Zendy; Yuko NEZAKI | Zendy; Eriko Kuno | Zendy; Ikuko Sugiyama | Zendy; Akifumi Mizutani | Zendy; Norihiro Tsukagoshi | Zendy

Open Access

Functional Roles of the Tissue Inhibitor of Metalloproteinase 3 (TIMP-3) during Ascorbate-induced Differentiation of Osteoblastic MC3T3-E1 Cells

Author(s) -

Hironao Suzuki,

Yuko NEZAKI,

Eriko Kuno,

Ikuko Sugiyama,

Akifumi Mizutani,

Norihiro Tsukagoshi

Publication year - 2003

Publication title -

bioscience biotechnology and biochemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.509

H-Index - 116

eISSN - 1347-6947

pISSN - 0916-8451

DOI - 10.1271/bbb.67.1737

Subject(s) - osteonectin , osteopontin , extracellular matrix , matrix metalloproteinase , alkaline phosphatase , chemistry , ascorbic acid , osteocalcin , microbiology and biotechnology , cellular differentiation , type i collagen , biochemistry , biology , gene , endocrinology , enzyme , food science

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.

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