Background and Objectives The transcription factor Fra-2 (Fosl2) is a member of the AP-1 complex and an important regulator of bone homeostasis. We have previously shown that Fra-2 controls bone development, osteoclas...
Background and Objectives The transcription factor Fra-2 (Fosl2) is a member of the AP-1 complex and an important regulator of bone homeostasis. We have previously shown that Fra-2 controls bone development, osteoclast size [1] and osteoblast differentiation through direct regulation of Collagen 1a2 and Osteocalcin (Ocn) [2]. Recent studies have established that the skeleton functions as an endocrine organ affecting metabolism through Ocn [3], although only few transcription factors and only one osteoblast-derived hormone are known to affect the crosstalk between bone and metabolism. Materials and Methods We have generated mice with specific deletion of Fra-2 ( Fosl2 ) or ectopic expression of Fra-2 in osteoblast to study the role of Fra-2 beyond the bone e.g. in metabolism. Results Here we show that mice with osteoblast specific deletion of Fra-2 ( Fosl2 ) have despite a low bone mass, an increased body weight. In contrast, ectopic expression of Fra-2 in osteoblasts display increased bone mass and decreased body weight accompanied with reduced serum glucose and insulin levels, improved glucose tolerance and insulin sensitivity. In addition, these Fra-2 mutant mice are protected from metabolic impairment, when challenged with high fat diet (HFD). Surprisingly a systemic inflammation and macrophage infiltration in liver, spleen and lung was observed in Fra-2 osteoblast specific mice. Mechanistically, we showed that in osteoblasts Fra-2 transcriptionally represses an important adipo-cytokine Adiponectin (Adipoq), while it induces Ocn, both responsible for the glucose and insulin metabolism alteration. Whereas, the systemic inflammation was likely due to the transcriptional increased of Osteopontin (OPN) expression by Fra-2, which is known as a potent inductor of macrophage activation. Conclusions Taking together these results show that Fra-2 expression in osteoblast transcriptionally modulates Adipoq, Ocn and OPN expression and secretion representing a novel mechanism
Smad family proteins are identified as intracellular signal mediators of the TGF-β *** this study,we identified two novel members of the Smad family,termed as AmphiSmad1/5/8 and AmphiSmad4,from Chinese *** AmphiSmad1...
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Smad family proteins are identified as intracellular signal mediators of the TGF-β *** this study,we identified two novel members of the Smad family,termed as AmphiSmad1/5/8 and AmphiSmad4,from Chinese *** AmphiSmad1/5/8 and AmphiSmad4 showed a typical domain structure of Smad proteins consisting of conserved MH1 and MH2 *** analysis placed AmphiSmad1/5/8 in the Smad1,5 and 8 subgroup of the R-Smad subfamily,and AmphiSmad4 in the Co-Smad *** spatial and temporal gene expression patterns of AmphiSmad1/5/8 and AmphiSmad4 showed that they may be involved in the embryonic development of notochord,myotome and alimentary canal,and may help to establish the specification of dorsal-ventral axis of ***,AmphiSmad1/5/8 and AmphiSmad4 showed extensive distribution in all adult tissues examined,suggesting that these two genes may play important roles in the morphogenesis of a variety of tissues especially notochord and gonad.
Nociceptive sensitization is a conserved form of neuronal plasticity that serves an important survival function, as it fosters behavior that protects damaged tissue during healing. This sensitization may involve a low...
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Prevailing knowledge dictates that naive αβ T cells require activation in lymphoid tissues before differentiating into effector or memory T cells capable of trafficking to nonlymphoid tissues. Here we demonstrate th...
Prevailing knowledge dictates that naive αβ T cells require activation in lymphoid tissues before differentiating into effector or memory T cells capable of trafficking to nonlymphoid tissues. Here we demonstrate that CD8+recent thymic emigrants (RTEs) migrated directly into the small intestine. CCR9, CCL25 and α4β7integrin were required for gut entry of CD8+RTEs. After T cell receptor stimulation, intestinal CD8+RTEs proliferated and acquired a surface phenotype resembling that of intraepithelial lymphocytes. CD8+RTEs efficiently populated the gut of lymphotoxin-α-deficient mice, which lack lymphoid organs. These studies challenge the present understanding of naive αβ T cell trafficking and suggest that RTEs may be involved in maintaining a diverse immune repertoire at mucosal surfaces.*Note: In the version of this article initially published, the vertical axis label ‘FITC’ is missing from the right column in Figure 1a. The correct figure is presented here. The error has been corrected in the PDF version of the article.
Annotating the functions of individual genes in in vivo contexts has become the primary task of mouse genetics in the postgenome era. In addition to conventional approaches using transgenic technologies and gene targe...
The vertebrate cranial vault, or calvaria, forms during embryonic development from cranial mesenchyme of multiple embryonic origins. Inductive interactions are thought to specify the number and location of the calvari...
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