TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts

Odontogenic tumors and cysts, arising in the jawbones, grow by resorption and destruction of the jawbones. However, mechanisms underlying bone resorption by odontogenic tumors/cysts remain unclear. Odontogenic tumors/cysts comprise odontogenic epithelial cells and stromal fibroblasts, which originate from the developing tooth germ. It has been demonstrated that odontogenic epithelial cells of the developing tooth germ induce osteoclastogenesis to prevent the tooth germ from invading the developing bone to maintain its structure in developing bones. Thus, we hypothesized that odontogenic epithelial cells of odontogenic tumors/cysts induce osteoclast formation, which plays potential roles in tumor/cyst outgrowth into the jawbone. The purpose of this study was to examine osteoclastogenesis by cytokines, focusing on transforming growth factor-β (TGF-β), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-κB ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1α (IL-1α) signaling and non-COX-2/PGE2 pathway through TGF-β receptor signaling. TGF-β1 and IL-1α produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma

Effects of CEACAM1 in oral keratinocytes on HO-1 expression induced by Candida β-glucan particles

Objective: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a member of the carcinoembryonic antigen family. Although its expression has been found in chronic oral inflammatory epithelium, this study aimed to know whether CEACAM1 in oral keratinocytes participates in host immune response against Candida albicans . Methodology: We investigated CEACAM1 expression in oral keratinocytes induced by C. albicans as well as by Candida cell wall component β-glucan particles (β-GPs). Furthermore, the effects of CEACAM1 on β-GPs-induced heme oxygenase-1 (HO-1) expression and its related signals were examined. Results: Fluorescence staining showed CEACAM1 expression in oral keratinocytes (RT7) cells, whereas quantitative reverse transcription (RT)-PCR indicated that both live and heat-killed C. albicans increased CEACAM1 mRNA expression in RT7 cells. Examinations using quantitative RT-PCR and western blotting indicated that CEACAM1 expression was also increased by β-GPs derived from C. albicans . Specific siRNA for CEACAM1 decreased HO-1 expression induced by β-GPs from C. albicans as well as the budding yeast microorganism Saccharomyces cerevisiae . Moreover, knockdown of CEACAM1 decreased β-GPs-induced ROS activity in the early phase and translocation of Nrf2 into the nucleus. Conclusion: CEACAM1 in oral keratinocytes may have a critical role in regulation of HO-1 for host immune defense during Candida infection

Physical Properties and Antimicrobial Release Ability of Gentamicin-Loaded Apatite Cement/α-TCP Composites: An In Vitro Study

Apatite cement (AC), which has excellent osteoconductive ability, and alpha-tricalcium phosphate (α-TCP), which can be used for bone replacement, are useful bone substitute materials. The objective of this study was to clarify the physical properties and antimicrobial release ability of antibiotic-loaded AC/α-TCP composites in vitro. Gentamicin-loaded, rapid setting AC/α-TCP composites were prepared in 2 mixing ratios (10:3 and 10:6). The cement paste of AC/α-TCP composites was prepared in a plastic mold and dried in a thermostatic chamber at 37 °C and 100% relative humidity for 24 h. A diametral tensile strength test, powder X-ray diffraction analysis, and gentamicin release test were performed. The diametral tensile strengths of the AC/α-TCP composites were significantly less than that of AC alone. Powder X-ray diffraction patterns exhibited the characteristic peaks of hydroxyapatite in the AC/α-TCP composites and gentamicin-loaded AC/α-TCP composites. The concentration of the released gentamicin was maintained above the minimum inhibitory concentration of Staphylococcus aureus until Day 30 in both the gentamicin-loaded AC/α-TCP composites (10:3 and 10:6). Our results suggest that a gentamicin-loaded AC/α-TCP composite has potential as a drug delivery system. Further study is essential to investigate the antimicrobial activity and safety of the gentamicin-loaded AC/α-TCP composites in animal models

Mouse Snail family transcription repressors regulate chondrocyte, extracellular matrix, type II collagen, and aggrecan.: Snail family and chondrocyte differentiation

International audienceSnail family genes are conserved among species during evolution and encode transcription factors expressed at different stages of development in different tissues. These genes are involved in a broad spectrum of biological functions: cell differentiation, cell motility, cell cycle regulation, and apoptosis. However, little is known about the target genes involved in these functions. Here we show that mouse Snail family members, Snail (Sna) and Slug (Slugh), are involved in chondrocyte differentiation by controlling the expression of type II collagen (Col2a1) and aggrecan. In situ hybridization analysis of developing mouse limb demonstrated that Snail and Slug mRNAs were highly expressed in hypertrophic chondrocytes. Inversely, the expression of collagen type II mRNA disappeared during hypertrophic differentiation. Snail and Slug mRNA expression was down-regulated during differentiation of the mouse chondrogenic cell line ATDC5 and overexpression of exogenous Snail or Slug in ATDC5 cells inhibited expression of collagen type II and aggrecan mRNA. Reporter analysis revealed Snail and Slug suppressed the promoter activity of Col2a1, and the E-boxes in the promoter region were the responsible element. Gel shift assay demonstrated the binding of Snail to the E-box. Because type II collagen and aggrecan are major functional components of extracellular matrix in cartilage, these results suggest an important role for Snail-related transcription repressors during chondrocyte differentiation