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Emdogain Stimulates Matrix Degradation by Osteoblasts

¹ Departments of Biochemistry, Orthodontics,
² Physiology, and
³ Internal Medicine, Osaka Dental University, 8-1 Kuzuha Hanazono-cho, Hirakata-shi, Osaka, 573-1121, Japan; and
⁴ Department of Laboratory Medicine and Pathology, Cancer Center, University of Minnesota, Minneapolis, USA

^* corresponding author, goda{at}cc.osaka-dent.ac.jp

Emdogain has been used clinically for periodontal regeneration, although the underlying molecular mechanisms are not clear at present. In this study, we hypothesized that Emdogain stimulated degradation of type I collagen via osteoblasts. We showed that Emdogain enhanced cell-mediated degradation of type I collagen in an MMP-dependent manner. Although MG-63 cells spontaneously produced a zymogen form of MMP-1, treatment with Emdogain significantly induced the generation of the active form of this enzyme. We demonstrated that MMP-3 was produced from MG63 cells in response to Emdogain in a MEK1/2-dependent manner. Concomitantly, blocking of MEK1/2 activation by U0126 significantly inhibited the generation of the active form of MMP-1 without affecting the total production of this collagenase. These results suggest that Emdogain facilitates tissue regeneration through the activation of the collagenase, MMP-1, that degrades matrix proteins in bone tissue microenvironments.

KEY WORDS: Emdogain • matrix metalloproteinases • osteoblasts