Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. of inflammation and bone resorption. was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and the calvarial bones were excised. RNA was isolated and analysed for transcript profiling using Murine GeneChip? arrays. Following infection, 2905 and 1234 genes in the infected calvarial bones and soft tissues, respectively, were differentially expressed ( 0.05). Biological pathways significantly impacted by infection in calvarial bone and calvarial tissue included leukocyte transendothelial migration, cell HOXA2 adhesion (immune system) molecules, cell cycle, extracellular matrixCreceptor interaction, focal adhesion, B-cell receptor signaling and transforming growth factor- signaling pathways resulting in proinflammatory, chemotactic effects, and T-cell stimulation. In conclusion, localized infection differentially induces transcription of a broad array of host genes, the profiles of which differed between inflamed calvarial bone and soft tissues. increases significantly in periodontal disease biofilms and is typically detected together with other pathogens and (Socransky & Haffajee, 2005). Furthermore, has been linked with endodontic infections, orofacial abscesses and periapical radiolucencies (Baumgartner as dominant member of pathogenic biofilms at sites of periodontal disease may contribute to the disease processes by elaborating components that can mediate adherence to mucosal surfaces, enable penetration into epithelial cells, affect host systems through specific cleavage of cell surface receptors, inhibit host defense mechanisms, elicit gingival tissue inflammation, and induce alveolar bone resorption. For example, chymotrypsin-like protease, phospholipase C, oligopeptidase, endopeptidase and cystalysin are defined factors with possible or confirmed roles in pathogenicity (Fenno & McBride, 1998; Chi to spleen, heart and brain following dental pulp infection in mice (Foschi studies have shown that components of can induce a range of proinflammatory cytokines, including interleukin 1 (IL-1), IL-1, tumor necrosis factor- (TNF-), 2,3-Butanediol IL-6 and IL-8, (Nixon studies have also shown that dentilisin, a major surface protease and virulence factor of role of these inflammatory molecules, as well as the broader aspects of the host response to in the periodontium, remains to be elucidated. Nonetheless, the capacity of to disrupt the normal activities of several immune response participants is well documented. Microarray analysis of the transcriptional host responses following exposure to bacterial and viral pathogens has become a powerful approach to improve understanding of the molecular basis of the host response to infections. Host response characterization has identified gene transcripts such as proinflammatory and anti-inflammatory responses uniquely affected by pathogens such as and (Joyce responses of host cells to challenge with or its virulence components in primary human coronary artery 2,3-Butanediol endothelial cells and human aortic endothelial cells (Chou lipo-oligosaccharide induced changes in the phosphorylation state and/or expression of gingival fibroblast intracellular signaling proteins, including Fos (Fos-c FBJ murine osteosarcoma oncoprotein-related transcription factor), MKK1 [mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) protein-serine kinase 1), MKK2 (MAPK/ERK protein-serine kinase 2), MKK3/6 (MAP kinase protein-serine kinase 3/6), nuclear factor-infection in mice using the calvarial model of inflammation and bone resorption. We performed a genome-wide transcriptional analysis of the calvarial bone and overlying soft tissues isolated from ATCC 35404 as described below following isoflurane inhalation anesthesia. All mouse infection procedures were performed in accordance with the approved guidelines set forth by the Institutional Animal Care and Use Committee at the University of Kentucky (Lexington, KY, USA). Bacteria and mouse infection The ATCC 35404 was cultured and maintained for the animal infections, which were within 15C30 min of bacterial preparation, as described previously (Kesavalu was injected at 1.5 109 cells (= 10 mice) into the soft tissues overlying the calvaria of the mice. Bacteria (suspended in 10 l of reduced transport fluid) were injected into the subcutaneous tissue over 2,3-Butanediol the right side of the parietal bone and anterior to the lambdoid suture once daily for 3 days using a Hamilton syringe (Hamilton Co., Reno, NV). An uninfected control group (= 10 mice) was injected with reduced transport fluid once daily for 3 days. Mice were sacrificed 8 h after the last injection by CO2 asphyxiation and cervical dislocation. The calvarial bone and overlying soft tissues from five mice in each group were excised, snap frozen.