Abstract
BackgroundMatrix metalloproteinases (MMPs) degrade the extracellular matrix (ECM) and regulate remodeling and regeneration of bone. Enamel matrix derivative (EMD) protein has been used clinically for periodontal regeneration, although its molecular mechanisms are not clear. We evaluated the role of matrix metalloproteinases (MMPs) in regulating EMD-dependent degradation of gelatin on oeoblast-like cell line MG63.MethodsMG-63 cells (osteoblast cell line) were incubated with 100 μg/ml EMD protein in the presence or absence of MMP-2 tissue inhibitor for 20 h followed by incubation on DQ-gelatin-coated plates for 4 h. MG-63 cells (1 × 106) were preincubated with SB203580 for 30 min at 37°C and were then placed in 100 μg/ml EMD protein for 24 h. Conditioned media were collected and detected by Western blot analysis.ResultsEMD protein enhanced cell-mediated degradation of gelatin, which was inhibited by the MMP inhibitor TIMP-2. Furthermore, MMP-2 was produced by MG63 cells in response to EMD protein in a P38 MAPK-dependent manner. In addition, blocking of p38 MAPK activation by SB203580 significantly inhibited generation of the active form of MMP-2.ConclusionP38 MAPK pathway promotes expression MMP-2 in EMD activated osteoblasts, which in turn stimulates periodontal regeneration by degrading matrix proteins in periodontal connective tissue.
Highlights
Matrix metalloproteinases (MMPs) degrade the extracellular matrix (ECM) and regulate remodeling and regeneration of bone
Enamel matrix derivative (EMD) protein-stimulated MG-63 cells promoted degradation of gelatin In order to determine whether EMD protein is able to facilitate osteoblast-mediated gelatin degradation, human osteoblasts were incubated in the presence or absence of 100 μg/ml EMD protein and plated on 100 μg/ml DQ-gelatin-coated plates as described in the Methods (Figure 1)
Because gelatin is a substrate for matrix metalloproteinases (MMPs), it is possible that tissue inhibitors of MMPs (TIMPs)-2 could inhibit cellmediated degradation of gelatin
Summary
Matrix metalloproteinases (MMPs) degrade the extracellular matrix (ECM) and regulate remodeling and regeneration of bone. Previous experimental models and clinical studies have shown that enamel matrix-derived (EMD) protein promotes generation of PDL, root cementum and alveolar bone [1,2,3]. EMD protein activates osteoblasts cells in vitro, leading to a wound-healing response [4] and generation of alkaline phosphatase [5]. Disturbed extracellular matrix (ECM) turnover leads to bone loss and its associated diseases, Mitogen-activated protein kinases (MAPKs) are important signal transducing enzymes involved in cellular regulation. Recent studies using a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor showed that cytokine stimulation of MMP-2 synthesis is involved in p38 MAPK signaling [11,12]
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