Article

MMP-3 provokes CTGF/CCN2 production independently of protease activity and dependently on dynamin-related endocytosis, which contributes to human dental pulp cell migration

  1. Koichiro Muromachi1,*,
  2. Naoto Kamio1,
  3. Takanori Narita2,
  4. Motoyo Annen-Kamio1,
  5. Hiroshi Sugiya2,
  6. Kiyoshi Matsushima1,3

Article first published online: 23 FEB 2012

DOI: 10.1002/jcb.24007

Issue

Journal of Cellular Biochemistry

Journal of Cellular Biochemistry

Volume 113, Issue 4, pages 1348–1358, April 2012

Additional Information

How to Cite

Muromachi, K., Kamio, N., Narita, T., Annen-Kamio, M., Sugiya, H. and Matsushima, K. (2012), MMP-3 provokes CTGF/CCN2 production independently of protease activity and dependently on dynamin-related endocytosis, which contributes to human dental pulp cell migration. J. Cell. Biochem., 113: 1348–1358. doi: 10.1002/jcb.24007

Author Information

  1. 1

    Department of Endodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan

  2. 2

    Department of Veterinary Biochemistry, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252-0880, Japan

  3. 3

    Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan

*Department of Endodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan.

Publication History

  1. Issue published online: 23 FEB 2012
  2. Article first published online: 23 FEB 2012
  3. Accepted manuscript online: 1 DEC 2011 11:15AM EST
  4. Manuscript Accepted: 18 NOV 2011
  5. Manuscript Received: 14 JUL 2011

Funded by

  • Japan Society for the Promotion of Science (JSPS). Grant Numbers: 20592239, 22791846
  • The Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). Grant Number: 2011-2013 (S1001024)

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Keywords:

  • MMP-3;
  • CTGF/CCN2;
  • DYNAMIN;
  • ENDOCYTOSIS;
  • CELL MIGRATION;
  • DENTAL PULP

Abstract

Matrix metalloproteinase-3 (MMP-3) expression is promoted after pulpotomy, and application of MMP-3 to dental pulp after pulpotomy accelerates angiogenesis and hard tissue formation. However, the mechanism by which MMP-3 promotes dental pulp wound healing is still unclear. Connective tissue growth factor/CCN family 2 (CTGF/CCN2), a protein belonging to the CCN family, is considered to participate in wound healing, angiogenesis, and cell migration. In this study, we examined the involvement of CTGF/CCN2 in MMP-3-induced cell migration in human dental pulp (fibroblast-like) cells. In human dental pulp cells, MMP-3 promoted cell migration, but this effect was clearly blocked in the presence of anti-CTGF/CCN2 antibody. MMP-3 provoked mRNA and protein expression and secretion of CTGF/CCN2 in a concentration- and time-dependent manner. The MMP-3 inhibitor NNGH failed to suppress MMP-3-induced CTGF/CCN2 protein expression. The potent dynamin inhibitor dynasore clearly inhibited MMP-3-induced CTGF/CCN2 expression. These results strongly suggest that MMP-3 induces CTGF/CCN2 production independently of the protease activity of MMP-3 and dependently on dynamin-related endocytosis, which is involved in cell migration in human dental pulp cells. J. Cell. Biochem. 113: 1348–1358, 2012. © 2011 Wiley Periodicals, Inc.

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