TGF-βRI kinase activity mediates Emdogain-stimulated in vitro osteoclastogenesis.

OBJECTIVES Emdogain, containing an extract of fetal porcine enamel matrix proteins, is a potent stimulator of in vitro osteoclastogenesis. The underlying molecular mechanisms are, however, unclear. MATERIAL AND METHODS Here, we have addressed the role of transforming growth factor-beta receptor type 1 (TGF-βRI) kinase activity on osteoclastogenesis in murine bone marrow cultures. RESULTS Inhibition of TGF-βRI kinase activity with SB431542 abolished the effect of Emdogain on osteoclastogenesis induced by receptor activator of nuclear factor kappa-B ligand or tumor necrosis factor-alpha. SB431542 also suppressed the Emdogain-mediated increase of OSCAR, a co-stimulatory protein, and dendritic cell-specific transmembrane protein and Atp6v0d2, the latter two being involved in cell fusion. Similar to transforming growth factor-beta1 (TGF-β), Emdogain could not compensate for the inhibition of IL-4 and IFNγ on osteoclast formation. When using the murine macrophage cell line RAW246.7, SB431542 and the smad-3 inhibitor SIS3 blocked Emdogain-stimulated expression of the transcription factor NFATc1. CONCLUSIONS Taken together, the data suggest that TGF-βRI kinase activity is necessary to mediate in vitro effects of Emdogain on osteoclastogenesis. CLINICAL RELEVANCE Based on these in vitro data, we can speculate that at least part of the clinical effects of Emdogain on osteoclastogenesis is mediated via TGF-β signaling.

Emdogain-regulated gene expression in palatal fibroblasts requires TGF-βRI kinase signaling.

Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI) kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI kinase, SB431542. Emdogain caused 39 coding genes to be differentially expressed in palatal fibroblasts by microarray analysis (p<0.05; >10-fold). Importantly, in the presence of the TGF-βRI kinase inhibitor SB431542, Emdogain failed to cause any significant changes in gene expression. Consistent with this mechanism, three independent TGF-βRI kinase inhibitors and a TGF-β neutralizing antibody abrogated the increased expression of IL-11, a selected Emdogain target gene. The MAPK inhibitors SB203580 and U0126 lowered the impact of Emdogain on IL-11 expression. The data support that TGF-βRI kinase activity is necessary to mediate the effects of Emdogain on gene expression in vitro.

Human IgA Fc receptor FcαRI (CD89) triggers different forms of neutrophil death depending on the inflammatory microenvironment

FcαRI (CD89), the human Fc receptor for IgA, is highly expressed on neutrophil granulocytes. In this study, we show that FcαRI induces different forms of neutrophil death, depending on the inflammatory microenvironment. The susceptibility of inflammatory neutrophils from sepsis or rheumatoid arthritis toward death induced by specific mAb, or soluble IgA at high concentrations, was enhanced. Although unstimulated cells experienced apoptosis following anti-FcαRI mAb stimulation, preactivation with cytokines or TLR agonists in vitro enhanced FcαRI-mediated death by additional recruitment of caspase-independent pathways, but this required PI3K class IA and MAPK signaling. Transmission electron microscopy of FcαRI-stimulated cells revealed cytoplasmic changes with vacuolization and mitochondrial swelling, nuclear condensation, and sustained plasma membrane. Coculture experiments with macrophages revealed anti-inflammatory effects of the partially caspase-independent death of primed cells following FcαRI engagement. Our data suggest that FcαRI has the ability to regulate neutrophil viability and to induce different forms of neutrophils depending on the inflammatory microenvironment and specific characteristics of the ligand-receptor interactions. Furthermore, these findings have potential implications for FcαRI-targeted strategies to treat neutrophil-associated inflammatory diseases.

Amîrā le-vêt Yaʿaqôv : anšprache an das hois Jaʿakov oder di drei bezondern pflichṭen jidišer ehefroien nida, ḥale, hadloke nach dem riṭuale ...

und ins daiṭše iberṭragen fon Zeligman Ber Bamberger

Ein maiśe fun kinig Arṭiś hof : wi er zich in zainm kinigraich hoṭ ṭun firn un waz er hoṭ gehoṭ fer monir un fun dem brimṭn riṭr Widwilṭ ...

Digitalisat der Ausg. Fjurda, 1780/81

Ein šin hisṭorie fun riṭr Zigmunṭ un Magdlina : fun einem machṭigi riṭr ... Zigmunṭ ... oich di šine printzesin Magdlina ... oiz Frankreich ...

Digitalisat der Ausg. Ovibach, [1713/14]

Riṣṣûy nikneset be- Ḥelqat Binyāmîn : le-ḥabbēr ham-maʿaśe be-middā we-qînā ašer lô nimṣā ʿôd ke-hinnē ; hen bi-ešôn ʿivrî ... ô' bi-lešôn aškenaz

[Benjamin Ben-David aus Kreilsheim]

Hoiz Jakov : kompendium unzerer riṭualien in der landesšprache ; fasṭ alle im gewehrlichen leben forkommenden religiezen broiche enḥaltṭend ...

heroisgegeben fon Moše ... Rozenṭhal

Uganda : a fhiziš-meṭriš-hisṭoriš un šṭaṭisṭiše bešraibung der land uganda wos iz unz angegeben fun di engliše regirung izṭ tzu grinden in jar a jidiše meluche

durch Ḥ. J. Buchbinder

Hans Karlinger und Josef Maria Riß: Bayerische Kunstgeschichte [Rezension]

Theodor Harburger

Warhafft- und eigentlich Geometrischer Grund-Riß, des alten Gräflichen Haus Serin-War, und der hernach neuerbauten Vestung Serin-War über der Traba liegend in Sclavonien : nach der Scala durch einen Inschienör in Grundriß gebracht

LS fec.

Warhafft- und eigentlich Geometrischer Grund-Riß, des alten Gräflichen Haus Serin-War, und der hernach neuerbauten Vestung Serin-War über der Traba liegend in Sclavonien : nach der Scala durch einen Inschienör in Grundriß gebracht

LS fec.

Grund-Riß von Ostende : samt kurzer Beschreibung der vorigen 1601 bis 1604 dreyjährigen, und der jetzigen 1706 drey Tägigen, Beläger- und glücklichen Erobeung[!] den 6. Julii

Dabei ein Porträtmedaillon von "Generalfeldmarschall von Overkerke"