Matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) in mature human odontoblasts and pulp tissue : the regulation of expressions of fibrillar collagens, MMPs and TIMPs by growth factors, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2)
1University of Oulu, Faculty of Medicine, Institute of Dentistry, Department of Oral and Maxillofacial Surgery
|Online Access:||PDF Full Text (PDF, 1.5 MB)|
|Persistent link:|| http://urn.fi/urn:isbn:9514270789
|Publish Date:|| 2003-08-15
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in Auditorium 1 of the Institute of Dentistry, on August 15th, 2003, at 1 p.m.
Professor Henry Magloire
Docent Olli Teronen
Dentin formation in physiological and pathological conditions has been widely studied, but the events and regulation are still not completely understood. Odontoblasts, terminally differentiated post-mitotic cells located in a single cell layer around pulp tissue, synthesize and mineralize dentin organic matrix. Growth factors, such as TGF-β1 and BMP-2, have been implicated in the regulation of the responses of odontoblasts and pulp tissue to external irritation. Matrix metalloproteinases (MMPs), a family of 28 endopeptidases collectively capable of degrading virtually all extracellular matrix components, and their specific tissue inhibitors (TIMPs) participate in the organo- and morphogenesis, physiological tissue turnover and pathological tissue destruction in many tissues, but very little is known about their presence, function, and regulation in the dentin-pulp complex cells and tissues. The aim of the work presented in this thesis was to analyze the expression and regulation of collagens, MMPs and TIMPs by TGF-β1 and BMP-2 in mature human odontoblasts and pulp tissue. Odontoblasts synthesize and secrete type I and type III collagens, with no clear effect of TGF-β1 on their expression levels. MMP-1, -2, -8, -9, -10, -11, -14, -15, -16, -19 and TIMP-1, -2, -3 and -4 were expressed by both odontoblasts and pulp tissue. MMP-3 and MMP-12 were not expressed in native odontoblasts or pulp tissue, and MMP-7, -24, and -25 were expressed only in odontoblasts. MMP-2, -10, -14, -20 and -23 were expressed more abundantly in odontoblasts, whereas pulp tissue expressed more MMP-13 and MMP-17. Growth factors differentially regulated the expression of different MMPs and TIMPs within and among the cells and tissues studied. In odontoblasts, MMP-1, -8 and -14 were down-regulated, but MMP-7, MMP-9, TIMP-1 and TIMP-3 up-regulated, by either TGF-β1 or BMP-2, alone or in combination. In pulp tissue, growth factors up-regulated the expression of MMP-1, -2, -10, -13, -17 and TIMP-3, but down-regulated TIMP-4. The widespread of expression of MMPs and TIMPs by mature human odontoblasts and pulp tissue suggests that they may participate in dentin matrix organization prior to mineralization, and that growth factors may further control dentin matrix modeling, not by regulating the synthesis of type I or III collagens as previously believed, but rather by differentially regulating each MMPs and TIMPs.
Acta Universitatis Ouluensis. D, Medica
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