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The pro-inflammatory and calcification effects of DMP-1 on pulp fibroblasts. Implications for the prevention of dental pulp calcifc metamorphosis Open Access


Other title
Osteocalcin in dental pulp inflammation
Osteopontin and dental pulp inflammation
Dentin Matrix protein-1 (DMP-1)
Preventive endodontics
Pulp inflammation
Dental pulp
Calcific metamorphosis
Traumatic dental injuries
Pulp calcification
Type of item
Degree grantor
University of Alberta
Author or creator
Abd-Elmeguid, Ashraf A.E.
Supervisor and department
Yu, Donald (Dentistry). Moqbel, Redwan (Pulmonary Medicine UofA, Immunology Uof Mannitoba)
Examining committee member and department
Kline, Loren (Dentistry)
Eggert, Michael (Dentistry)
Lacy, Paige (Pulmonary Medicine)
Vliagoftis, Harissios (Pulmonary Medicine)
Huang, George (Endodontics, Boston Unversity)
Medical Sciences-Dentistry

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Traumatic dental injuries are very common in the first and second decades of life. Trauma, if severe, could result in irreversible changes such as root resorption and/or partial or complete pulp obliteration by hard tissue. Dental pulp calcific metamorphosis is the rapid calcification of the pulp soft tissue in response to trauma. It is characterised by the deposition of dentin-like and bone-like tissues inside the dental pulp. Total avulsion of teeth represents almost 16% of dental traumatic injuries where the replantation of teeth back into their socket is the first treatment of choice. Inflammatory cells and osteoclasts were reported in teeth replantation cases, highlighting the role of inflammation in this type of calcification. Accordingly, the hypothesis of the current research was that dental pulp calcification and inflammation are closely integrated mechanisms. The immuno-histochemical localisation of a calcification molecule, dentin matrix protein (DMP-1), in pulp inflammation was performed. This was followed by determining its possible role in mediating inflammation by testing its induction of interleukin-6 (IL-6) and IL-8 expression in pulp fibroblasts. This proinflammatory effect is enhanced using lipopolysaccharide (LPS). The inhibitor of p38 mitogen activated protein kinase (p38MAPK) (SB-203580) blocked this effect. Osteopontin (OPN) and osteocalcin (OCN) were also examined for their expression in pulp inflammation using western blot and immuno-histochemistry respectively. Vascular endothelial growth factor (VEGF) increased in response to OPN stimulation of pulp cells. DMP-1 induced the expression of OPN, OCN, alkaline phosphatase (AP) and VEGF. p38MAPK inhibitor decreased DMP-1- induced OPN, AP and VEGF to their normal expression. Recombinant human DMP-1 showed marked calcification of ferret dental pulp chambers and DMP-1 was localised at 2 and 6 weeks following the replantation of ferret premolars. In vivo blocking of the inflammatory effect of DMP-1 using p38MAPK inhibitor significantly decreased calcification inside the dental pulp at 2 and 6 weeks post replantation. It is concluded that the DMP-1 is involved in the development of calcific metamorphosis partly through its pro inflammatory effect. DMP-1 also promoted pulp cells proliferation, pro-inflammation, and angiogenesis. Our data demonstrate a novel therapeutic strategy by which dental pulp inflammation and calcification are prevented at the same time.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Abd-Elmeguid A, Yu DC, Kline LW, Moqbel R, Vliagoftis H. Dentin matrix protein-1 activates dental pulp fibroblasts. Journal of endodontics 2012;38(1):75-80.

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