Bordoni Valentina, Reina Giacomo, Orecchioni Marco, Furesi Giulia, Thiele Stefanie, Gardin Chiara, Zavan Barbara, Cuniberti Gianaurelio, Bianco Alberto, Rauner Martina, Delogu Lucia G
Stimulation of bone formation by monocyte-activator functionalized graphene oxide in vivo Journal Article
In: Nanoscale, vol. 11, no. 41, pp. 19408–19421, 2019, ISSN: 2040-3372.
Abstract | Links | BibTeX | Tags: Animals, Biocompatible Materials, Bone Morphogenetic Protein 2, Calcium Phosphates, Cell Differentiation, Cell Survival, Coculture Techniques, Graphite, Humans, I2CT, Inbred C57BL, Male, Mesenchymal Stem Cells, Mice, Monocytes, Oncostatin M, Osteoblasts, Osteogenesis, Signal Transduction, Team-Bianco, Tibia, Wnt Proteins
@article{bordoni_stimulation_2019,
title = {Stimulation of bone formation by monocyte-activator functionalized graphene oxide in vivo},
author = {Valentina Bordoni and Giacomo Reina and Marco Orecchioni and Giulia Furesi and Stefanie Thiele and Chiara Gardin and Barbara Zavan and Gianaurelio Cuniberti and Alberto Bianco and Martina Rauner and Lucia G Delogu},
doi = {10.1039/c9nr03975a},
issn = {2040-3372},
year = {2019},
date = {2019-11-01},
journal = {Nanoscale},
volume = {11},
number = {41},
pages = {19408--19421},
abstract = {Nanosystems are able to enhance bone regeneration, a complex process requiring the mutual interplay between immune and skeletal cells. Activated monocytes can communicate pro-osteogenic signals to mesenchymal stem cells and promote osteogenesis. Thus, the activation of monocytes is a promising strategy to improve bone regeneration. Nanomaterials specifically selected to provoke immune-mediated bone formation are still missing. As a proof of concept, we apply here the intrinsic immune-characteristics of graphene oxide (GO) with the well-recognized osteoinductive capacity of calcium phosphate (CaP) in a biocompatible nanomaterial called maGO-CaP (monocytes activator GO complexed with CaP). In the presence of monocytes, the alkaline phosphatase activity and the expression of osteogenic markers increased. Studying the mechanisms of action, we detected an up-regulation of Wnt and BMP signaling, two key osteogenic pathways. The role of the immune activation was evidenced by the over-production of oncostatin M, a pro-osteogenic factor produced by monocytes. Finally, we tested the pro-osteogenic effects of maGO-CaP in vivo. maGO-CaP injected into the tibia of mice enhanced local bone mass and the bone formation rate. Our study suggests that maGO-CaP can activate monocytes to enhance osteogenesis ex vivo and in vivo.},
keywords = {Animals, Biocompatible Materials, Bone Morphogenetic Protein 2, Calcium Phosphates, Cell Differentiation, Cell Survival, Coculture Techniques, Graphite, Humans, I2CT, Inbred C57BL, Male, Mesenchymal Stem Cells, Mice, Monocytes, Oncostatin M, Osteoblasts, Osteogenesis, Signal Transduction, Team-Bianco, Tibia, Wnt Proteins},
pubstate = {published},
tppubtype = {article}
}
Parietti Véronique, Monneaux Fanny, Décossas Marion, Muller Sylviane
Function of CD4+,CD25+ Treg cells in MRL/lpr mice is compromised by intrinsic defects in antigen-presenting cells and effector Ŧ cells Journal Article
In: Arthritis and Rheumatism, vol. 58, no. 6, pp. 1751–1761, 2008, ISSN: 0004-3591.
Abstract | Links | BibTeX | Tags: Animal, Animals, Antigen-Presenting Cells, Antigens, B7-1 Antigen, B7-2 Antigen, CD, Cell Communication, Cells, Coculture Techniques, CTLA-4 Antigen, Cultured, Disease Models, Female, I2CT, Interleukin-1, Interleukin-2 Receptor alpha Subunit, Lupus Erythematosus, Mice, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier
@article{parietti_function_2008,
title = {Function of CD4+,CD25+ Treg cells in MRL/lpr mice is compromised by intrinsic defects in antigen-presenting cells and effector Ŧ cells},
author = {Véronique Parietti and Fanny Monneaux and Marion Décossas and Sylviane Muller},
doi = {10.1002/art.23464},
issn = {0004-3591},
year = {2008},
date = {2008-06-01},
journal = {Arthritis and Rheumatism},
volume = {58},
number = {6},
pages = {1751--1761},
abstract = {OBJECTIVE: Naturally occurring CD4+,CD25+ Treg cells are central in the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells is involved in the emergence of autoimmunity. We undertook this study to analyze relative proportions and functional alterations of Treg cells in MRL/lpr mice.
METHODS: The frequency of CD4+,CD25+ T cells in the peripheral blood of healthy and autoimmune mice was compared by flow cytometry. The capacity of CD4+,CD25+ T cells to inhibit the proliferation and cytokine secretion of CD4+,CD25- T cells was assessed after polyclonal activation.
RESULTS: MRL/lpr mice exhibited a normal percentage of CD4+,CD25 high T cells, and forkhead box P3 messenger RNA and protein expression in Treg cells was not altered. However, MRL/lpr Treg cells displayed a reduced capacity to suppress proliferation and to inhibit interferon-gamma secretion by syngeneic effector CD4+,CD25- T cells, as compared with syngeneic cocultures of CBA/J T cells. Moreover, effector MRL/lpr CD4+,CD25- T cells were substantially less susceptible to suppression even when cultured with CBA/J or MRL/lpr Treg cells. Crossover experiments led us to conclude that in MRL/lpr mice, each partner engaged in T cell regulation displays altered functions. Molecules involved in suppressive mechanisms (CTLA-4 and CD80/CD86) are underexpressed, and antigen-presenting cells (APCs) produce raised levels of interleukin-6, which is known to abrogate suppression.
CONCLUSION: Our results suggest that although the frequency and phenotype of Treg cells in MRL/lpr mice are similar to those in normal mice, Treg cells in MRL/lpr mice are not properly stimulated by APCs and are unable to suppress proinflammatory cytokine secretion from effector T cells.},
keywords = {Animal, Animals, Antigen-Presenting Cells, Antigens, B7-1 Antigen, B7-2 Antigen, CD, Cell Communication, Cells, Coculture Techniques, CTLA-4 Antigen, Cultured, Disease Models, Female, I2CT, Interleukin-1, Interleukin-2 Receptor alpha Subunit, Lupus Erythematosus, Mice, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Monneaux F, Muller S
Laboratory protocols for the identification of Th cell epitopes on self-antigens in mice with systemic autoimmune diseases Journal Article
In: Journal of Immunological Methods, vol. 244, no. 1-2, pp. 195–204, 2000, ISSN: 0022-1759.
Abstract | Links | BibTeX | Tags: Animals, Antigen Presentation, Antigen-Presenting Cells, Autoantigens, B-Lymphocytes, Coculture Techniques, Epitopes, Female, Flow Cytometry, I2CT, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Lymphocyte Activation, Mice, Monneaux, Ribonucleoproteins, Small Nuclear, Systemic, T-Lymphocyte, Team-Dumortier, Th1 Cells, Th2 Cells
@article{monneaux_laboratory_2000,
title = {Laboratory protocols for the identification of Th cell epitopes on self-antigens in mice with systemic autoimmune diseases},
author = {F Monneaux and S Muller},
doi = {10.1016/s0022-1759(00)00256-8},
issn = {0022-1759},
year = {2000},
date = {2000-10-01},
journal = {Journal of Immunological Methods},
volume = {244},
number = {1-2},
pages = {195--204},
abstract = {T cells play a critical role in both the immunological and clinical manifestations of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). Although in normal mice multiple T cell epitopes have been characterized in several self-proteins, there is little information on the fine specificity of autoreactive T cells in lupus model mice and humans. In SLE-prone mice and humans, the only Th cell epitopes identified at the molecular level in self-antigens concern histones and nucleosomes, and the 70-kD U1-snRNP protein. T cell characterization in certain autoimmune mice such as MRL lpr/lpr and NZB/NZW mice has been largely impaired by their hyporesponsiveness in response to mitogen and minimal IL-2 secretion. In addition, MRL lpr/lpr mice also develop lymphadenopathy characterized by the progressive accumulation of functionally immature CD4(-) CD8(-) T cells. It is therefore important to optimize the methods used to measure T cell proliferation and cytokine production ex vivo in order to identify minimal activation in the presence of appropriate antigen. The protocol described in this article has been used for identifying in young MRL lpr/lpr and NZB/NZW mice a CD4(+) T cell epitope in the murine 70-kD U1-RNP protein.},
keywords = {Animals, Antigen Presentation, Antigen-Presenting Cells, Autoantigens, B-Lymphocytes, Coculture Techniques, Epitopes, Female, Flow Cytometry, I2CT, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Lymphocyte Activation, Mice, Monneaux, Ribonucleoproteins, Small Nuclear, Systemic, T-Lymphocyte, Team-Dumortier, Th1 Cells, Th2 Cells},
pubstate = {published},
tppubtype = {article}
}