Publications
2019
Vargas-Franco Jorge William, Castaneda Beatriz, Gama Andrea, Mueller Christopher G, Heymann Dominique, Rédini Françoise, Lézot Frédéric
Genetically-achieved disturbances to the expression levels of TNFSF11 receptors modulate the effects of zoledronic acid on growing mouse skeletons Article de journal
Dans: Biochemical Pharmacology, vol. 168, p. 133–148, 2019, ISSN: 1873-2968.
Résumé | Liens | BibTeX | Étiquettes: 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}
}
2015
Lézot Frédéric, Chesneau Julie, Navet Benjamin, Gobin Bérengère, Amiaud Jérome, Choi YongWon, Yagita Hideo, Castaneda Beatriz, Berdal Ariane, Mueller Christopher G, Rédini Françoise, Heymann Dominique
Skeletal consequences of RANKL-blocking antibody (IK22-5) injections during growth: mouse strain disparities and synergic effect with zoledronic acid Article de journal
Dans: Bone, vol. 73, p. 51–59, 2015, ISSN: 1873-2763.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibodies, Bone Density Conservation Agents, Bone Development, Bone resorption, Diphosphonates, Female, Imidazoles, Inbred C57BL, Mice, Newborn, Pregnancy, RANK ligand, RANKL, Side effect, Skeleton growth, Team-Mueller, Tooth Eruption, Zoledronic acid
@article{lezot_skeletal_2015,
title = {Skeletal consequences of RANKL-blocking antibody (IK22-5) injections during growth: mouse strain disparities and synergic effect with zoledronic acid},
author = {Frédéric Lézot and Julie Chesneau and Benjamin Navet and Bérengère Gobin and Jérome Amiaud and YongWon Choi and Hideo Yagita and Beatriz Castaneda and Ariane Berdal and Christopher G Mueller and Françoise Rédini and Dominique Heymann},
doi = {10.1016/j.bone.2014.12.011},
issn = {1873-2763},
year = {2015},
date = {2015-01-01},
journal = {Bone},
volume = {73},
pages = {51--59},
abstract = {High doses of bone resorption inhibitors are currently under evaluation in pediatric oncology. Previous works have evidenced transient arrest in long bone and skull bone growth and tooth eruption blockage when mice were treated with zoledronic acid (ZOL). The question of potential similar effects with a RANKL-blocking antibody (IK22.5) was raised. Sensitivity disparities in these inhibitors between mouse strains and synergic effects of zoledronic acid and a RANKL-blocking antibody were subsidiary questions. In order to answer these questions, newborn C57BL/6J and CD1 mice were injected every two or three days (4 injections in total so 7 or 10 days of treatment length) with high doses of a RANKL-blocking antibody. The consequences on the tibia, craniofacial bones and teeth were analyzed by μCT and histology at the end of the treatment and one, two and three months later. The results obtained showed that RANKL-blocking antibody injections induced a transient arrest of tibia and skull bone growth and an irreversible blockage of tooth eruption in C57BL/6J mice. In CD1 mice, tooth eruption defects were also present but only at much higher doses. Similar mouse strain differences were obtained with zoledronic acid. Finally, a synergic effect of the two inhibitors was evidenced. In conclusion as previously observed for bisphosphonates (ZOL), a RANKL-blocking antibody induced a transient arrest in long bone and skull bone growth and a blockage of tooth eruption with however disparities between mouse strains with regard to this last effect. A synergic effect of both bone resorption inhibitors was also demonstrated.},
keywords = {Animals, Antibodies, Bone Density Conservation Agents, Bone Development, Bone resorption, Diphosphonates, Female, Imidazoles, Inbred C57BL, Mice, Newborn, Pregnancy, RANK ligand, RANKL, Side effect, Skeleton growth, Team-Mueller, Tooth Eruption, Zoledronic acid},
pubstate = {published},
tppubtype = {article}
}