The roles of cytokines in bacteria induced bone resorption : interaction of RANKL with TNF and IL-1 in endodontic lesion; the impact of CC-chemokines on inflammatory bone
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TNF and IL-1 have long been recognized as potent pro-inflammatory cytokines in osteoclastogenesis. The present study examined the expression of key osteoclastogenic factor, RANKL, in endodontic lesions and its interdependent relationship with TNF and IL-1. The experiments were conducted using IL-1RI-/-, TNFRp55-/- -P75-/- and matched wild type mice. Dental pulp was surgically exposed and inoculated with a mixture of six common endodontic pathogens for O to 5 weeks. Specimens were immunohistochemically stained usmg a RANKL N-19 mAb to examine RANKL expression; H &E stained sections were used to quantify inflammatory cell infiltration and endodontic lesion formation and TRAP analysis to measure osteoclastogenesis. Statistical significance was determined by one-way ANOVA. Results showed that RANKL expression is significantly higher in either TNF or IL-1 receptor ablated mice compared to the wild type mice (P[less than]0.001), which is statistically correlated with inflammatory cell infiltration (correlation coefficiency factor r[greater than]0.7). The density of osteoclasts is consistent with the intensity of RANKL expression (correlation coefficiency factor r [greater than]0.8). These findings suggest that RANKL might be essential in endodontic lesion formation, and compensatory to the absence of TNF, but less to IL-1. The ablation of TNF signaling was more important than the ablation of IL-1 receptor signaling in compromising the efficacy of RANKL and the potency of osteoclast. The result also implicates a potential mechanism that the recruitment of osteoclastic progenitors and the inflammatory up-regulation of RANKL facilitate the initiation of dental internal resorption. Although the indispensable roles of CC chemokines in host defense against microbial infection have been well established, the exact modulation of their involvement between innate and acquired immunity and their contribution to bone resorption remain unclear. This study was conducted to explore how two major chemokines, MCP-1 and MIP-1[alpha], determine the process of inflammatory response and their distinct roles in acquired immunity. A murine calvarium model with introduced Porphyromonas gingivalis antigen challenge was used to evaluate the impacts of inflammation on bone resorption and soft tissue destruction. The involvement of acquired immunity was introduced by having test objects immunized against the challenging agent before bacterial challenge. MCP-1-/-, MIP-1[alpha]-/- and matched wild type mice were tested. Histological analysis was performed to examine the process of pathogenesis and expressmg molecule profile was identified at RNA level by RNase protection assay. In innate immunity, the ablation of MCP-1 and MIP-1[alpha] equally resulted in reduced resistance to bacterial challenge and compensatory inflammatory activities. However, the absence Of MCP-1 or MIP-1[alpha] showed no difference in contributing bone resorption. With acquired immunity, the positive correlation of acquired immunity and bone resorption was confirmed. Nevertheless, MCP-1 and MIP-1[alpha] played the opposite roles in regulating acquired immunity that the ablation of MCP-1 led to decreased bone resorption and proinflammatory responses while the ablation of MIP-1[alpha] was stimulatory to bone resorption and pro-inflammatory activities with the involvement of acquired immunity. It was shown that the ablation of MCP-1 and MIP-1[alpha] Were differently functioning in innate and acquired immunity in terms of pro-inflammatory activities and bacteria induced bone resorption.
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact email@example.com.Thesis (D.Sc.D.)--Boston University, Goldman School of Dental Medicine, 2005 (Endodontics).Includes bibliographic references (leaves 98-118).
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