This report shows that interleukin (IL) 17–producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR) 6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor β and IL-6 additionally need IL-1 and neutralization of interferon (IFN) γ and IL-4 for CCR6 expression. Forced expression of RORγt, a key transcription factor for Th17 cell differentiation, induces not only IL-17 but also CCR6 in naive T cells. Furthermore, Th17 cells produce CCL20, the known ligand for CCR6. Synoviocytes from arthritic joints of mice and humans also produce a large amount of CCL20, with a significant correlation (P = 0.014) between the amounts of IL-17 and CCL20 in RA joints. The CCL20 production by synoviocytes is augmented in vitro by IL-1β, IL-17, or tumor necrosis factor α, and is suppressed by IFN-γ or IL-4. Administration of blocking anti-CCR6 monoclonal antibody substantially inhibits mouse arthritis. Thus, the joint cytokine milieu formed by T cells and synovial cells controls the production of CCL20 and, consequently, the recruitment of CCR6+ arthritogenic Th17 cells to the inflamed joints. These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA.

A simulated body fluid (SBF) with ion concentrations approximately equal to those of human blood plasma has been used widely for in vitro assessment of the bioactivity of artificial materials and for the formation of bone-like apatite on various substrates. The ion concentrations of a conventional SBF (c-SBF) are, however, not exactly equal to those of blood plasma. In the present study, a revision of c-SBF was made to prepare new SBFs (r-SBF, i-SBF, and m-SBF) with ion concentrations equal to or closer to those of blood plasma. The ion concentrations of the r-SBF and i-SBF were designed to be equal to those of blood plasma in total and dissociated amounts, respectively. The m-SBF was designed to have a total ion concentration equal to that of blood plasma, except for the concentration of HCO(-) (3), which was set to the saturated level with respect to calcite. The ion concentrations and pH of the as-prepared new SBFs were found to be equal to those of the nominal values. Upon sealed storage, the r-SBF and i-SBF showed no change in ion concentrations for up to 4 weeks at 5 degrees C, and up to 2 weeks at 36.5 degrees C, but thereafter they showed a decrease in HCO(-) (3) concentration and an increase in pH. Under the same storage conditions, the c-SBF and m-SBF showed no change in ion concentrations and pH values over a period of up to 8 weeks. These results indicate that the r-SBF and i-SBF are less stable than the c-SBF and m-SBF in terms of changes in ion concentrations relative to storage period. The m-SBF is optimal for in vitro bioactivity assessment of artificial materials and for biomimetic production of bone-like apatite.

A simple chemical method was established for inducing bioactivity of Ti and its alloys. When pure Ti, Ti-6A1-4V, Ti-6A1-2Nb-Ta, and Ti-15Mo-5Zr-3A1 substrates were treated with 10M NaOH aqueous solution and subsequently heat-treated at 600 degrees C, a thin sodium titanate layer was formed on their surfaces. Thus, treated substrates formed a dense and uniform bonelike apatite layer on their surfaces in simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. This indicates that the alkali- and heat-treated metals bond to living bone through the bonelike apatite layer formed on their surfaces in the body. The apatite formation on the surfaces of Ti and its alloys was assumed to be induced by a hydrated titania which was formed by an ion exchange of the alkali ion in the alkali titanate layer and the hydronium ion in SBF. The resultant surface structure changed gradually from the outermost apatite layer to the inner Ti and its alloys through a hydrated titania and titanium oxide layers. This provides not only the strong bonding of the apatite layer to the substrates but also a uniform gradient of stress transfer from bone to the implants. The present chemical surface modification is therefore expected to allow the use the bioactive Ti and its alloys as artificial bones even under load-bearing conditions.

During the past decade, zirconia-based ceramics have been successfully introduced into the clinic to fabricate fixed dental prostheses (FDPs), along with a dental computer-aided/computer-aided manufacturing (CAD/CAM) system. In this article (1) development of dental ceramics, (2) the current status of dental CAD/CAM systems, (3) CAD/CAM and zirconia restoration, (4) bond between zirconia and veneering ceramics, (5) bond of zirconia with resin-based luting agents, (6) surface finish of zirconia restoration and antagonist enamel wear, and (7) clinical evaluation of zirconia restoration are reviewed. Yttria partially stabilized tetragonal zirconia polycrystalline (Y-TZP) showed better mechanical properties and superior resistance to fracture than other conventional dental ceramics. Furthermore, ceria-stabilized tetragonal zirconia polycrystalline and alumina nanocomposites (Ce-TZP/A) had the highest fracture toughness and had resistance to low-temperature aging degradation. Both zirconia-based ceramics have been clinically available as an alternative to the metal framework for fixed dental prostheses (FDPs). Marginal adaptation of zirconia-based FDPs is acceptable for clinical application. The most frequent clinical complication with zirconia-based FDPs was chipping of the veneering porcelain that was affected by many factors. The mechanism for the bonding between zirconia and veneering ceramics remains unknown. There was no clear evidence of chemical bonding and the bond strength between zirconia and porcelain was lower than that between metal and porcelain. There were two alternatives proposed that might avoid chipping of veneering porcelains. One was hybrid-structured FDPs comprising CAD/CAM-fabricated porcelain parts adhering to a CAD/CAM fabricated zirconia framework. Another option was full-contour zirconia FDPs using high translucent zirconia. Combined application of silica coating and/or silane coupler, and 10-methacryloyloxydecyl dihydrogen phosphate is currently one of the most reliable bonding systems for zirconia. Adhesive treatments could be applied to luting the restorations and fabricating hybrid-structured FDPs. Full-contour zirconia FDPs caused concern about the wear of antagonist enamel, because the hardness of Y-TZP was over double that of porcelain. However, this review demonstrates that highly polished zirconia yielded lower antagonist wear compared with porcelains. Polishing of zirconia is possible, but glazing is not recommended for the surface finish of zirconia. Clinical data since 2010 are included in this review. The zirconia frameworks rarely got damaged in many cases and complications often occurred in the veneering ceramic materials. Further clinical studies with larger sample sizes and longer follow-up periods are required to investigate the possible influencing factors of technical failures.

The transcription factor Sox9 is expressed in all chondroprogenitors and has an essential role in chondrogenesis. Sox9 is also expressed in other tissues, including central nervous system, neural crest, intestine, pancreas, testis, and endocardial cushions, and plays a crucial role in cell proliferation and differentiation in several of these tissues. To determine the cell fate of Sox9-expressing cells during mouse embryogenesis, we generated mice in which a Cre recombinase gene preceded by an internal ribosome entry site was inserted into the 3 untranslated region of the Sox9 gene (Sox9-Cre knock-in). In the developing skeleton, Sox9 was expressed before Runx2, an early osteoblast marker gene. Cell fate mapping by using Sox9-Cre;ROSA26 reporter (R26R) mice revealed that Sox9-expressing limb bud mesenchymal cells gave rise to both chondrocytes and osteoblasts. Furthermore, a mutant in which the Osterix gene was inactivated in Sox9-expressing cells exhibited a lack of endochondral and intramembranous ossification and a lack of mature osteoblasts comparable with Osterix-null mutants. In addition, Sox9-expressing limb bud mesenchymal cells also contributed to tendon and synovium formation. By using Sox9-Cre;R26R mice, we also were able to systematically follow Sox9-expressing cells from embryonic day 8.0 to 17.0. Our results showed that Sox9-expressing cells contributed to the formation of all cell types of the spinal cord, epithelium of the intestine, pancreas, and mesenchyme of the testis. Thus, our results strongly suggest that all osteo-chondroprogenitor cells, as well as progenitors in a variety of tissues, are derived from Sox9-expressing precursors during mouse embryogenesis.imb skeleton is formed as a cartilage model that undergoes endochondral bone formation. At the initiation of limb development, undifferentiated mesenchymal cells in the lateral plate mesoderm receive proliferation signals from the apical ectodermal ridge. These cells start to aggregate and form mesenchymal condensations, which are the primordia of the limb skeleton, then differentiate into chondrocytes and generate a cartilage skeleton. Cells surrounding the nascent cartilage form the perichondrium and periosteum, specialized structures consisting of thin layers of mesenchymal cells. The cells surrounding the zone of hypertrophic chondrocytes begin to differentiate into osteoblasts and, together with blood vessels and osteoclasts, invade the mineralized cartilage matrix and replace cartilage by bone.Specific transcription factors regulate the differentiation pathways of chondrocytes and osteoblasts. Sox9, a transcription factor with a high-mobility group DNA-binding domain, activates chondrocyte-specific marker genes, such as Col2a1, Col11a2, and Aggrecan (1-3). Sox9 is expressed in all chondroprogenitors and chondrocytes except hypertrophic chondrocytes (4, 5). Campomelic dysplasia, a human disease that is caused by heterozygous mutations in the Sox9 gene, is characterized by a general hypoplasia of endochondral bones (6, 7). We have re...