Experimental studies on effects of orthodontic forces in generation of immune responses : possible roles for immunoregulating molecules in the control of alveolar bone remodeling
Author: AL-Hashimi, Najat AL-Sayed
Date: 2004-08-26
Location: Föreläsningssalen M63, plan 6, Karolinska Universitetssjukhuset, Huddinge
Time: 9.30
Department: Institutionen för medicin / Department of Medicine
Abstract
The transformation of orthodontic forces to periodontal tissues involves
several biological mechanisms, which ultimately result in bone
remodelling. It has been suggested that the immune system plays a role in
the regulation of bone remodelling through production of immune mediators
by inflammatory cells that have migrated from dilated periodontal
ligament capillaries after the application of orthodontic force. In vivo
induction of potentially important immunoregulatory mediators and
co-stimulatory molecules were studied in response to orthodontic force to
investigate their role in bone resorption.
The maxillary right first molar of Wistar male rats was moved mesially by means of a closed coil spring ligated to the mesial aspect of the first molar. A strain of 500mN was applied. The maxillary contralateral molars served as controls. Using in situ hybridization with radioactive synthetic oligoneocleotide probes and immunochemistry, the induction of the pro-inflammatory cytokines IL1beta, IL-6, TNF-alpha, IFN-gamma and the anti-inflammatory cytokines IL-4 and IL-10 was examined. Also, the expression of potential chemokines as macrophage inflammatory protein-2 (MIP2), monocyte chemotactic protein-1 (MCP-1), and Regulated upon Activation, Normal Tcell Expressed and Secreted (RANTES) was studied. In addition, the role of the co-stimulatory molecules CD40 and CD40 ligand in periodontal and bone cells in orthodontically treated and untreated teeth was investigated.
We demonstrated that the expression of IL-1beta mRNA and IL-6 mRNA in periodontal and bone cells located on the pressure side reached a high level on day 3 after application of the mechanical force. The numbers of cells expressing IL-1beta and IL-6 mRNA decreased on day 7, and that expression became undetectable on day 10. The control side showed little induction of IL-1beta and IL-6 mRNA. In contrast, messenger RNA for TNF-alpha was undetectable during the whole study. Thus, certain cytokines play an important role in bone remodeling after orthodontic tooth movement in the pressure zone. Furthermore, there was induction of MIP-2, MCP-1, and RANTES mRNA in response to orthodontic tooth movement on the pressure side. The maximum induction of MCP-1 and RANTES was detected on day 3. Expression of MCP-1 mRNA dominated, followed by RANTES mRNA and then MIP-2 mRNA. The number of MCP-1, RANTES and MIP-2 positive cells declined on day 7 and on day 10. This suggests that chemokines have a potential role in recruiting cells from the monocyte/macrophage cell line to the pressure zone during orthodontic movement, which may contribute to the regulation of bone remodeling.
The induction of IFN-gamma was significantly higher in the experimental side than the contralateral control side and peaked on day 7, but remained high on day 10. IL-4 and IL-10 were not detected during examined time-points neither in pressure nor in contralateral control side. Considering the potential immunoregulatory roles played by IFN-gamma, the data suggest that IFN-gamma may be involved in periodontium remodeling during orthodontic tooth movement. A further proof of an adaptive immune response was the identification of CD40+ as well as CD40L expressing cells peaking at day 3 after trauma.
The maxillary right first molar of Wistar male rats was moved mesially by means of a closed coil spring ligated to the mesial aspect of the first molar. A strain of 500mN was applied. The maxillary contralateral molars served as controls. Using in situ hybridization with radioactive synthetic oligoneocleotide probes and immunochemistry, the induction of the pro-inflammatory cytokines IL1beta, IL-6, TNF-alpha, IFN-gamma and the anti-inflammatory cytokines IL-4 and IL-10 was examined. Also, the expression of potential chemokines as macrophage inflammatory protein-2 (MIP2), monocyte chemotactic protein-1 (MCP-1), and Regulated upon Activation, Normal Tcell Expressed and Secreted (RANTES) was studied. In addition, the role of the co-stimulatory molecules CD40 and CD40 ligand in periodontal and bone cells in orthodontically treated and untreated teeth was investigated.
We demonstrated that the expression of IL-1beta mRNA and IL-6 mRNA in periodontal and bone cells located on the pressure side reached a high level on day 3 after application of the mechanical force. The numbers of cells expressing IL-1beta and IL-6 mRNA decreased on day 7, and that expression became undetectable on day 10. The control side showed little induction of IL-1beta and IL-6 mRNA. In contrast, messenger RNA for TNF-alpha was undetectable during the whole study. Thus, certain cytokines play an important role in bone remodeling after orthodontic tooth movement in the pressure zone. Furthermore, there was induction of MIP-2, MCP-1, and RANTES mRNA in response to orthodontic tooth movement on the pressure side. The maximum induction of MCP-1 and RANTES was detected on day 3. Expression of MCP-1 mRNA dominated, followed by RANTES mRNA and then MIP-2 mRNA. The number of MCP-1, RANTES and MIP-2 positive cells declined on day 7 and on day 10. This suggests that chemokines have a potential role in recruiting cells from the monocyte/macrophage cell line to the pressure zone during orthodontic movement, which may contribute to the regulation of bone remodeling.
The induction of IFN-gamma was significantly higher in the experimental side than the contralateral control side and peaked on day 7, but remained high on day 10. IL-4 and IL-10 were not detected during examined time-points neither in pressure nor in contralateral control side. Considering the potential immunoregulatory roles played by IFN-gamma, the data suggest that IFN-gamma may be involved in periodontium remodeling during orthodontic tooth movement. A further proof of an adaptive immune response was the identification of CD40+ as well as CD40L expressing cells peaking at day 3 after trauma.
List of papers:
I. Alhashimi N, Frithiof L, Brudvik P, Bakhiet M (2001). "Orthodontic tooth movement and de novo synthesis of proinflammatory cytokines." Am J Orthod Dentofacial Orthop 119(3): 307-12
Pubmed
II. Alhashimi N, Frithiof L, Brudvik P, Bakhiet M (1999). "Chemokines are upregulated during orthodontic tooth movement. " J Interferon Cytokine Res 19(9): 1047-52
Pubmed
III. Alhashimi N, Frithiof L, Brudvik P, Bakhiet M (2000). "Orthodontic movement induces high numbers of cells expressing IFN-gamma at mRNA and protein levels. " J Interferon Cytokine Res 20(1): 7-12
Pubmed
IV. Alhashimi N, Frithiof L, Brudvik P, Bakhiet M (2004). "CD40-CD40L expression during orthodontic tooth movement in rats. " Angle Orthod 74(1): 100-5
Pubmed
I. Alhashimi N, Frithiof L, Brudvik P, Bakhiet M (2001). "Orthodontic tooth movement and de novo synthesis of proinflammatory cytokines." Am J Orthod Dentofacial Orthop 119(3): 307-12
Pubmed
II. Alhashimi N, Frithiof L, Brudvik P, Bakhiet M (1999). "Chemokines are upregulated during orthodontic tooth movement. " J Interferon Cytokine Res 19(9): 1047-52
Pubmed
III. Alhashimi N, Frithiof L, Brudvik P, Bakhiet M (2000). "Orthodontic movement induces high numbers of cells expressing IFN-gamma at mRNA and protein levels. " J Interferon Cytokine Res 20(1): 7-12
Pubmed
IV. Alhashimi N, Frithiof L, Brudvik P, Bakhiet M (2004). "CD40-CD40L expression during orthodontic tooth movement in rats. " Angle Orthod 74(1): 100-5
Pubmed
Issue date: 2004-08-05
Publication year: 2004
ISBN: 91-7349-985-4
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