The Role of Tumor Necrosis Factor Receptor Type 1 in Orthodontic Tooth Movement

Orthodontic tooth movement is dependent on osteoclast activity. Tumor necrosis factor (TNF)-α plays an important role, directly or via chemokine release, in osteoclast recruitment and activation. This study aimed to investigate whether the TNF receptor type 1 (p55) influences these events and, consequently, orthodontic tooth movement. An orthodontic appliance was placed in wild-type mice (WT) and p55-deficient mice (p55−/−). Levels of TNF-α and 2 chemokines (MCP-1/CCL2, RANTES/CCL5) were evaluated in periodontal tissues. A significant increase in CCL2 and TNF-α was observed in both groups after 12 hrs of mechanical loading. However, CCL5 levels remained unchanged in p55−/− mice at this time-point. The number of TRAP-positive osteoclasts in p55−/− mice was significantly lower than that in WT mice. Also, there was a significantly smaller rate of tooth movement in p55−/− mice. Analysis of our data suggests that the TNFR-1 plays a significant role in orthodontic tooth movement that might be associated with changes in CCL5 levels.

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Microenvironmental Factors and The Role Of Tumor Necrosis Factor Receptor Type 1 (TNFR-1) In Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v122.21.4149.4149 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4149-4149

Author(s):

Claudia Duerr ◽

Angela Schulz ◽

Sibylle Ohl ◽

Thorsten Zenz ◽

Stephan Stilgenbauer ◽

...

Keyword(s):

B Cells ◽

Chronic Lymphocytic Leukemia ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Lymphocytic Leukemia ◽

Receptor Type ◽

Tnf Α ◽

Necrosis Factor

Abstract B-cell Chronic Lymphocytic Leukemia (CLL) represents the most common leukemia among adults in the western world and remains still incurable. CLL is characterized by the accumulation of malignant B-cells in the peripheral blood and the lymphoid organs due to apoptosis resistance. Removing the cells from their physiological microenvironment spontaneously drives them into apoptosis in vitro unless they are supported by bystander cells (e.g. stromal cells or accessory leukocytes) or soluble factors such as cytokines produced by these cells. In order to identify differences in the biology of healthy B-cells and the leukemic clones we performed comparative microarray analyses of both cell types before and after cultivation in high cell density that allows cell-cell interactions of CLL cells with accessory leukocytes. These studies revealed the establishment of an inflammatory microenvironment in CLL characterized by the transcriptional upregulation of several cytokines. Antibody array analyses of culture supernatants and blood serum samples confirmed the upregulation of these proteins and their relevance for CLL. The 11 most deregulated cytokines were quantified in the serum of 250 CLL patients of the German CLL8 study cohort and 50 age- and sex-matched controls in order to identify novel predictive or prognostic markers. Bioinformatical analyses of the data are currently ongoing. Among other proteins, we found Tumor Necrosis Factor Receptor Type 1 (TNFR-1) to be significantly upregulated in the malignant B-cells under survival-maintaining cultivation as well as in CLL serum, but not in healthy controls (Figure 1). To exploit the difference in TNFR-1 biology, we treated CLL cells with TNF-α in combination with wogonin which is known to block the survival supporting pathway propagated by TNFR-1 upon TNF-α binding. This combinational treatment strategy effectively triggered Disclosures: No relevant conflicts of interest to declare.

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