Yoshimitsu Abiko

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Caveolin is an essential and signature protein of caveolae. Caveolin-1 participates in signal transduction processes by acting as a scaffolding protein that concentrates, organizes and functional regulates signalling molecules within caveolar membranes. Beta-tricalcium phosphate (β-TCP) has been widely used for scaffold in tissue engineering due to its high biodegradability, osteoconductivity, easy manipulation, and lack of histotoxicity. To better understand the role of caveolin-1 in bone homeostasis and response to β-TCP scaffold, β-TCP was implanted into the dog mandible defects in beagle dogs, and gene expression profiles were examined focused on the molecular components involved in caveolin-1 regulation. Here we showed the quantitative imageology analysis characterized using in vivo micro-computed tomography (CT) images at 4 and 7 days after β-TCP implanted in dog mandibles. The bone reformation by using the β-TCP scaffolds began within 4 days of surgery, and was healing well at 7 days after surgery. Higher mRNA level of caveolin-1 was observed in β-TCP-implanted Beagle dog mandibles compared with controls at day 4 and day 7 post-surgery. The enhancement of caveolin-1 by β-TCP was further confirmed by immunohistochemistry and immunofluorescence analysis. We further revealed increased Smad7 and Phospho Stat3 expression in β-TCP-implanted specimens. Taken together, these results suggest that the enhancement of caveolin-1 play an important role in accelerating bone formation by β-TCP. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

J Oral Pathol Med (2012) 41: 769–778Background:  Oral epithelial cells significantly influence host inflammatory responses against Candida albicans in oropharyngeal candidiasis. Pro‐inflammatory cytokines function as an early innate immune system mediator during C. albicans infection in oral epithelial cells. We sought to elucidate the pattern of the molecular mechanisms governing the human gingival epithelial cells (HGECs) to C. albicans infection likely involve multiple converging signal transduction pathways.Materials and methods:  Primary HGECs were cultured with C. albicans ATCC90029. Total RNA was extracted after 8 h of infection and monitored mRNA levels using Affymetrix GeneChip (Human Genome U133 plus 2.0 Array, 48 000 genes). GeneChip data was analyzed by GeneSpring software and Ingenuity Pathway Analysis system. Reverse transcription polymerase chain reaction (RT‐PCR), real‐time RT‐PCR and immunohistochemistry were used to investigate gene expression changes.Results:  The differentially expressed genes represented functions as diverse as immune response and inflammatory disease. IL‐8, ICAM‐1 and Cox‐2 showed a greater than two fold change in expression relative to those in control cells. Altered mRNA levels in GeneChip analysis were confirmed by RT‐PCR and real‐time RT‐PCR. Stronger immunoreactivity against ICAM‐1 and Cox‐2 was also observed in the infection with C. albicans in rat gingival epithelium. We have identified differential gene expression up‐regulated or down‐regulated with the up‐regulation of IL‐8 in C. albicans‐treated cells.Conclusion:  These findings indicate that the molecular mechanisms underlying the IL‐8 response of HGECs to C. albicans infection likely involve multiple converging signal transduction pathways.