Role of Innate Inflammation in the Regulation of Tissue Remodeling during Tooth Eruption

Abstract

Tooth eruption is characterized by a coordinated complex cascade of cellular and molecular events that promote tooth movement through the eruptive pathway. During tooth eruption, the stratum intermedium structurally changes to the papillary layer with tooth organ development. We previously reported intercellular adhesion molecule-1 (ICAM-1) expression on the papillary layer, which is the origin of the ICAM-1-positive junctional epithelium. ICAM-1 expression is induced by proinflammatory cytokines, including interleukin-1 and tumor necrosis factor. Inflammatory reactions induce tissue degradation. Therefore, this study aimed to examine whether inflammatory reactions are involved in tooth eruption. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed sequential expression of hypoxia-induced factor-1α, interleukin-1β, and chemotactic factors, including keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2), during tooth eruption. Consistent with the RT-PCR results, immunohistochemical analysis revealed KC and MIP-2 expression in the papillary layer cells of the enamel organ from the ameloblast maturation stage. Moreover, there was massive macrophage and neutrophil infiltration in the connective tissue between the tooth organ and oral epithelium during tooth eruption. These findings suggest that inflammatory reactions might be involved in the degradation of tissue overlying the tooth organ. Further, these reactions might be induced by hypoxia in the tissue overlying the tooth organ, which results from decreased capillaries in the tissue. Our findings indicate that bacterial infections are not associated with the eruption process. Therefore, tooth eruption might be regulated by innate inflammatory mechanisms.

Keywords: HIF-1; IL-1; KC; neutrophil; tooth eruption.

Figure 1

The expression of intercellular adhesion molecule-1 (ICAM-1) during the tooth organ development at 7 days postnatal (dPN) (a), 14 dpN (b), and 19 PN (c,d). (a) No clear expression of ICAM-1 was detected in the tooth organ. (b) ICAM-1 was detected at the papillary layer cells (arrowheads). (c) Strong reactions of ICAM-1 expression were also detected in the papillary layer (arrowheads). (d) Higher magnification of the enamel organ at 19 dPN. ICAM-1 expressed in blood vessels (arrows) in addition to the papillary layer (arrowheads). Bars = 200 μm in (a–c); 50 μm in (d).

Figure 2

Analysis of the mRNA expression of Mm00468869_m1 (HIF-1α), Mm01336189_m1 (IL-1β), macrophage inflammatory protein-2 (MIP-2), and keratinocyte-derived chemokine (KC) using reverse transcription-polymerase chain reaction (RT-PCR) (n = 9 in each group). In general, the mRNA expression of these four molecules was significantly increased during the tooth eruption. (* p < 0.05).

Figure 3

Immunohistochemical detection of KC (a) and MIP-2 (b) in the tooth organ at 14 dPN. Both chemokines were expressed in the papillary layer (arrowheads) and adjacent odontogenic epithelial cells over the tooth organs (asterisk). Bars = 50 μm.

Figure 4

Localization of macrophages during the tooth eruption at 7 dPN (a,b), 14 dPN (c,d), and 19 dPN (e,f). Many residential macrophages were detected in the dental pulp in all stages (asterisks). From 14 dPN, macrophages were easily detected in the connective tissue overlying the tooth organ (d,f, arrowheads). Bars = 200 μm in (a,c,e); 50 μm in (b,d,f).

Figure 5

Localization of neutrophils during the tooth eruption at 7dPN (a,b), 14 dPN (c,d), and 19 dPN (e,f). No neutrophils were detected in the dental pulp in all stages. At 14 dPN, neutrophils were easily detected in the connective tissue overlying the tooth organ ((d), arrowheads), and the number of neutrophils were increased at 19 dPN ((f), arrowheads). Bars = 200 μm in (a,c,e); 50 μm in (b,d,f).