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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
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- Author / Creator
- Abd-Elmeguid, Ashraf A.E.
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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. -
- Graduation date
- Fall 2012
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- Type of Item
- Thesis
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- Degree
- Doctor of Philosophy
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- License
- This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.