HMGB1-induced inflammatory response promotes bone healing in murine tooth extraction socket.

High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 has been suggested to mediate various inflammatory diseases. However, it is still unknown whether HMGB1 is involved in a healing process in the tooth extraction socket, the tissue containing gingival epithelium, and alveolar bone that is exposed to oral bacteria. In this study, we constructed a murine tooth extraction model with anti-HMGB1 neutralization antibody administration and observed the inflammatory response and bone healing process in tooth extraction sockets by molecular imaging of myeloperoxidase (MPO) activity, histological analysis, and quantitative RT-PCR. The translocation of HMGB1 from the nucleus to the cytoplasm in gingival epithelial cells and inflammatory cells was inhibited by anti-HMGB1 antibody administration. The MPO activity around the tooth extraction socket was significantly reduced, and the numbers of CD31- and CD68-positive cells were significantly lower in the anti-HMGB1 antibody treatment samples than in the control samples. The TRAP-positive cells, osteocalcin positive cells, and the neoplastic bone area were significantly lower in anti-HMGB1 antibody treatment samples than in control samples. The expression levels of IL-1ß and VEGF-A were also decreased in anti-HMGB1 antibody treatment samples compared to that in control samples. Secreted HMGB1 induced initial acute inflammation and inflammatory cells recruitment after tooth extraction. HMGB1 was associated with angiogenesis and bone remodeling by osteoclast and osteoblast activation and promoted bone healing in the tooth extraction socket.

Differential expression of immunologic proteins in gingiva after socket preservation in mini pigs.

UNLABELLED: During healing following tooth extraction, inflammation and the immune response within the extraction socket are related to bone resorption. OBJECTIVE: We sought to identify how the alloplastic material used for socket preservation affects the immune responses and osteoclastic activity within extraction sockets. MATERIAL AND METHODS: Using a porcine model, we extracted teeth and grafted biphasic calcium phosphate into the extraction sockets. We then performed a peptide analysis with samples of gingival tissue from adjacent to the sockets and compared the extraction only (EO) and extraction with socket preservation (SP) groups. We also used real-time polymerase chain reaction (PCR) to evaluate the expression level of immunoglobulins, chemokines and other factors related to osteoclastogenesis. Differences between the groups were analyzed for statistical significance using paired t tests. RESULTS: Levels of IgM, IgG and IGL expression were higher in the EO group than in the SP group 1 week post-extraction, as were the levels of CCL3, CCL5, CXCL2, IFN-γ and TNF-α expression (p < 0.05). In addition, receptor activator of nuclear factor kappa-B ligand (RANKL) was also significantly upregulated in the EO group (p < 0.05), as were IL-1ß, IL-6 and IL-8 (p < 0.05). CONCLUSIONS: These results suggest that the beneficial effect of socket preservation can be explained by suppression of immune responses and inflammation.

Effects of saliva on early post-tooth extraction tissue repair in rats.

The aim of the present study was to perform a biochemical, histological, and histomorphometrical evaluation of the mechanisms involved in tissue repair in rats subjected to submandibulectomy-induced hyposialia, 24, 48, and 72 hours of post-tooth extraction. We studied the correlation between the lack of submandibular saliva and the modulation of inflammatory mediators involved in tissue repair, such as prostaglandin E2 , nitric oxide (NO), and tumor necrosis factor alpha (TNF-α). Rats with hyposialia showed a delay in socket healing, slow replacement of the clot with granulation tissue, and fewer cells and collagen fibers, concomitant with a longer inflammatory process, as compared to controls. The lack of saliva induced by submandibulectomy modified the levels of prostaglandin E2 , NO, and TNF-α, and tissue response in the early stages of wound healing compared to controls, and could thus determine alterations in later osteogenic response. Our results allow concluding that hyposialia modulates the parameters of inflammation studied here, and that it is essential for optimal healing. Therefore, these findings provide evidence for the importance of submandibular saliva to final bone socket healing.

Spatial and temporal localization of secretory IgA in healing tooth extraction sockets in a rabbit model.

PURPOSE: The purpose of this study was to look at the spatial and temporal localization of secretory IgA in healing tooth extraction sockets in a rabbit model. MATERIALS AND METHODS: Twenty-four male New Zealand White rabbits were used in the study. Incisor teeth were extracted from both jaws, and the healing extraction socket with the surrounding jaw bone was harvested at 48 hours, 4 days, and 1, 2, 4, 8, 12, and 16 weeks. Tissues were fixed, decalcified, and processed for hematoxylin and eosin and immunohistochemical staining. The sections were stained to detect secretory IgA. The stained sections were then imaged, and an automated computer program was used to detect the brown 3,3'-diaminobenzidine stain that represented the secretory IgA. The data were obtained in the form of percentage area and intensity of stain and analyzed using analysis of variance (Tukey-Kramer and Scheffé's tests). RESULTS: Spatial and temporal differences in localization of secretory IgA were observed across time frames in both jaws. CONCLUSION: The results of this study showed definite trends in the spatial and temporal localization of secretory IgA in healing tooth extraction sockets in a rabbit model.

Neutrophils in the molar tooth extraction wound in the rat: a transmission electron microscope (TEM) study.

Neutrophils have been ascribed a number of functions from ultrastructural studies of healing wounds. All of the wounds so far examined have been relatively aseptic. This study investigates, by TEM, the structure of neutrophils in healing molar tooth sockets in rats. Prior to epithelial coverage, a dense infiltrate of neutrophils separated the viable wound tissues from the overlying debris and bacteria. The more deeply situated neutrophils contained many granules and only occasional phagosomes. More superficial neutrophils contained fewer granules and phagosomes with engulfed bacteria undergoing lysis. The most superficial neutrophils were degenerate, lacked granules and often contained viable bacteria. There were varying numbers of neutrophils containing granules in the blood clot, granulation tissue, wound epithelium and adjacent tissue. No extracellular neutrophil granules nor extracellular discharge of granules was found. These findings differ from those of previous ultrastructural studies of relatively aseptic healing wounds. Ultrastructurally, the only function of neutrophils in healing tooth extraction wounds appears to be phagocytosis of bacteria, which supports a role in the prevention of infection.