Publications
2019
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}
}
Vargas-Franco Jorge William, Castaneda Beatriz, Gama Andrea, Mueller Christopher G, Heymann Dominique, Rédini Françoise, Lézot Frédéric
In: Biochemical Pharmacology, vol. 168, pp. 133–148, 2019, ISSN: 1873-2968.
Abstract | Links | BibTeX | Tags: Animals, Bone Density Conservation Agents, Bone Development, Craniofacial bone, Gene Knockout Techniques, Growth, Inbred C57BL, Knockout, Long bone, Mice, Newborn, Osteoprotegerin, RANK ligand, RANKL/RANK/OPG, Skull, Team-Mueller, Tibia, Tooth, X-Ray Microtomography, Zoledronic acid
@article{vargas-franco_genetically-achieved_2019,
title = {Genetically-achieved disturbances to the expression levels of TNFSF11 receptors modulate the effects of zoledronic acid on growing mouse skeletons},
author = {Jorge William Vargas-Franco and Beatriz Castaneda and Andrea Gama and Christopher G Mueller and Dominique Heymann and Françoise Rédini and Frédéric Lézot},
doi = {10.1016/j.bcp.2019.06.027},
issn = {1873-2968},
year = {2019},
date = {2019-10-01},
journal = {Biochemical Pharmacology},
volume = {168},
pages = {133--148},
abstract = {Zoledronic acid (ZOL), a nitrogen bisphosphonate (N-BP), is currently used to treat and control pediatric osteolytic diseases. Variations in the intensity of the effects and side effects of N-BPs have been reported with no clear explanations regarding their origins. We wonder if such variations could be associated with different levels of RANKL signaling activity in growing bone during and after the treatment with N-BPs. To answer this question, ZOL was injected into neonate C57BL/6J mice with different genetically-determined RANKL signaling activity levels (Opg+/+textbackslashRankTg-, Opg+/+textbackslashRankTg+, Opg+/-textbackslashRankTg-, Opg+/-textbackslashRankTg+, Opg-/-textbackslashRankTg- and Opg-/-textbackslashRankTg+ mice) following a protocol (4 injections from post-natal day 1 to 7 at the dose of 50 μg/kg) that mimics those used in onco-pediatric patients. At the end of pediatric growth (1 and half months) and at an adult age (10 months), the bone morphometric and mineral parameters were measured using μCT in the tibia and skull for the different mice. A histologic analysis of the dental and periodontal tissues was also performed. At the end of pediatric growth, a delay in long bone and skull bone growth, a blockage of tooth eruption, some molar root alterations and a neoplasia-like structure associated with incisor development were found. Interestingly, the magnitude of these side effects was reduced by Opg deficiency (Opg-/-) but increased by Rank overexpression (RankTg). Analysis of the skeletal phenotype at ten months confirmed respectively the beneficial and harmful effects of Opg deficiency and Rank overexpression. These results validated the hypothesis that the RANKL signaling activity level in the bone microenvironment is implicated in the modulation of the response to ZOL. Further studies will be necessary to understand the underlying molecular mechanisms, which will help decipher the variability in the effects of N-BPs reported in the human population. SIGNIFICANT STATEMENTS: The present study establishes that in mice the RANKL signaling activity level is a major modulator of the effects and side-effects of bisphosphonates on the individual skeleton during growth. However, the modulatory actions are dependent on the ways in which this level of activity is increased. A decrease in OPG expression is beneficial to the skeletal phenotype observed at the end of growth, while RANK overexpression deteriorates it. Far removed from pediatric treatment, in adults, the skeletal phenotypes initially observed at the end of growth for the different levels of RANKL signaling activity were maintained, although significant improvement was associated only with reductions in OPG expression.},
keywords = {Animals, Bone Density Conservation Agents, Bone Development, Craniofacial bone, Gene Knockout Techniques, Growth, Inbred C57BL, Knockout, Long bone, Mice, Newborn, Osteoprotegerin, RANK ligand, RANKL/RANK/OPG, Skull, Team-Mueller, Tibia, Tooth, X-Ray Microtomography, Zoledronic acid},
pubstate = {published},
tppubtype = {article}
}