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Staquet M.J.,CNRS Lyon Institute of Functional Genomics
Advances in dental research

Initial sensing of infection is mediated by germline-encoded pattern-recognition receptors (PRRs), the activation of which leads to the expression of inflammatory mediators responsible for the elimination of pathogens and infected cells. PRRs act as immune sensors that provide immediate cell responses to pathogen invasion or tissue injury. Here, we review the expression of PRRs in human dental pulp cells, namely, receptors from the Toll-like (TLR) and Nod-like NLR families, by which cells recognize bacteria. Particular attention is given to odontoblasts, which are the first cells encountered by pathogens and represent, in the tooth, the first line of defense for the host. Understanding cellular and molecular mechanisms associated with the recognition of bacterial pathogens by odontoblasts is critical for the development of therapeutic strategies that aim at preventing excessive pulp inflammation and related deleterious effects. Source

Laudet V.,CNRS Lyon Institute of Functional Genomics
Current Biology

Metamorphosis, classically defined as a spectacular post-embryonic transition, is well exemplified by the transformation of a tadpole into a frog. It implies the appearance of new body parts (such as the limbs), the resorption of larval features (such as the tail) and the remodelling of many organs (such as the skin or the intestine). In vertebrates, metamorphosis has been well characterized in anuran amphibians, where thyroid hormones orchestrate the intricate and seemingly contradictory changes observed at the cellular and tissue levels. Thyroid hormones control a complex hierarchical cascade of target genes via binding to specific receptors, TRα and TRβ, ligand-activated transcription factors belonging to the nuclear receptor superfamily. Metamorphosis is actually widespread in the vertebrates, though quite diverse in the way it manifests in a particular species. Furthermore, evolutionary and ecological variations of this key event, from paedomorphosis to direct development, provide an excellent illustration of how tinkering with a control pathway can lead to divergent life histories. The study of invertebrate chordates has also shed light on the origin of metamorphosis. The available data suggest that post-embryonic remodelling governed by thyroid hormones is an ancestral feature of chordates. According to this view, metamorphosis of the anurans is an extreme example of a widespread life history transition. © 2011 Elsevier Ltd. All rights reserved. Source

Bleicher F.,CNRS Lyon Institute of Functional Genomics
Experimental Cell Research

Odontoblasts are post-mitotic cells organized as a layer of palisade cells along the interface between the dental pulp and dentin. They are responsible for the formation of the physiological primary and secondary dentins. They synthesize the organic matrix of type I collagen and actively participate to its mineralization by secreting proteoglycans and non-collagenous proteins that are implicated in the nucleation and the control of the growth of the mineral phase. They also participate to the maintenance of this hard tissue throughout the life of the tooth by synthesizing reactionary dentin in response to pathological conditions (caries, attrition, erosion. . .).Besides these fundamental dentinogenic activities, odontoblasts were recently suspected to play a role as sensor cells. They are able to sense the bacteria invasion during caries and then to initiate the pulp immune and inflammatory response. They are also well equipped in ion channels implicated in mechanotransduction or nociception which make odontoblasts suitable candidates to sense external stimuli and to mediate tooth pain sensation. © 2013 Elsevier Inc. Source

Gallet M.,CNRS Lyon Institute of Functional Genomics | Vanacker J.-M.,CNRS Lyon Institute of Functional Genomics
Trends in Endocrinology and Metabolism

The bone fragility and increased fracture risk associated with osteoporosis in post-menopausal women is a major public health concern. Current treatments for osteoporosis relying on hormone replacement therapies are suspected to have an association with increased breast cancer risk, highlighting the need for identifying new potential targets in bone. Recent data suggest that the estrogen-related receptor (ERR)α, an orphan nuclear receptor, represses osteoblast differentiation, and that its deletion in knockout mouse models results in increased mineral density. Furthermore, modulation of ERRα activity reduces proliferation and tumorigenesis of breast cancer cells. These results indicated that inhibition of ERRα might provide a treatment for osteoporosis without displaying adverse effects in breast cancer. This review focuses on the role of the ERR receptors, and in particular ERRα, in the differentiation of bone precursor cells and its consequences on bone homeostasis, and discusses the possible grounds for the discrepancies reported in the literature. © 2010 Elsevier Ltd. Source

Flamant F.,CNRS Lyon Institute of Functional Genomics | Gauthier K.,CNRS Lyon Institute of Functional Genomics
Biochimica et Biophysica Acta - General Subjects

Background: Thyroid hormone receptors TRα1, TRβ1 and TRβ2 are broadly expressed and exert a pleiotropic influence on many developmental and homeostatic processes. Extensive genetic studies in mice precisely defined their respective function. Scope of review: The purpose of the review is to discuss two puzzling issues:The isoform specificity problem: the different functions of TRα1, TRβ1 and TRβ2 might reflect either their different distribution in tissues or differences in the receptor intrinsic properties.The cell-specificity problem: one would expect that different cell types share a common repertoire of TR target genes, but current knowledge does not support this assumption. How TR function is affected by the cellular context is an unsolved question. Major conclusions: Mouse genetics support a balanced contribution of expression pattern and receptor intrinsic properties in defining the receptor respective functions. The molecular mechanisms sustaining cell specific response remain hypothetical and based on studies performed with other nuclear receptors. General significance: The isoform-specificity and cell-specificity questions have many implications for clinical research, drug development, and endocrine disruptor studies. This article is part of a Special Issue entitled Thyroid hormone signalling. © 2012 Elsevier B.V. All rights reserved. Source

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