Docteur BENOIT GOBRON

Thèses universitaires

• Hormones intestinales et remodelage osseux

  2020

  Gut hormone and bone remodeling

  Physiologie, physiopathologie, biologie systémique médicale🎓 Angers

  Direction : Béatrice Bouvard, Guillaume Mabilleau

Source : catalogue national des thèses theses.fr (ABES). Ne couvre que les doctorats / HDR — les thèses d'exercice (DES) sont archivées dans les SCD universitaires.

Publications académiques en France

Articles déposés en accès libre sur l'archive ouverte des universités françaises (HAL) — gage d'activité de recherche en France.

• Development of a First‐in‐Class Unimolecular Dual GIP / GLP ‐2 Analogue, GL ‐0001, for the Treatment of Bone Fragility

  2023

  ArticleJournal of Bone and Mineral Research

• Développement et rechute synchrone d’un myélome multiple et d’un carcinome rénal à cellules claires

  2020

  ArticleRevue du Rhumatisme

• Enteroendocrine K Cells Exert Complementary Effects to Control Bone Quality and Mass in Mice

  2020

  ArticleJournal of Bone and Mineral Research

• Efficacy of targeting bone-specific GIP receptor in ovariectomy-induced bone loss

  2018

  ArticleJournal of endocrinology

• Incretin-based therapy for the treatment of bone fragility in diabetes mellitus

  2018

  ArticlePeptides

Source : HAL — archive ouverte CCSD/CNRS (couvre articles, chapitres EMC, communications congrès, thèses).

Lieu de consultation

• RHUMATHOLOGIE DR GOBRON

  24 RUE DES PERREYEUX, 49800 Trélazé

  Libéral

Tarifs & secteur de conventionnement

Prendre rendez-vous & contact

Lien Doctolib = recherche Google site:doctolib.fr (le 1er résultat est presque toujours le profil correct s'il existe).

Top publications · les plus citées

• 1

  Development of a First-in-Class Unimolecular Dual GIP/GLP-2 Analogue, GL-0001, for the Treatment of Bone Fragility

  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023

  📚 20 citations🎯 RCR 3.31Top 14% NIH🔓 Open Access📄 PDF gratuit ↗

  Lire l'abstract Crossref ↓

  ABSTRACT Due to aging of the population, bone frailty is dramatically increasing worldwide. Although some therapeutic options exist, they do not fully protect or prevent against the occurrence of new fractures. All current drugs approved for the treatment of bone fragility target bone mass. However, bone resistance to fracture is not solely due to bone mass but relies also on bone extracellular matrix (ECM) material properties, i.e., the quality of the bone matrix component. Here, we introduce the first-in-class unimolecular dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-2 (GIP/GLP-2) analogue, GL-0001, that activates simultaneously the glucose-dependent insulinotropic polypeptide receptor (GIPr) and the glucagon-like peptide-2 receptor (GLP-2r). GL-0001 acts synergistically through a cyclic adenosine monophosphate-lysyl oxidase pathway to enhance collagen maturity. Furthermore, bilateral ovariectomy was performed in 32 BALB/c mice at 12 weeks of age prior to random allocation to either saline, dual GIP/GLP-2 analogues (GL-0001 or GL-0007) or zoledronic acid groups (n = 8/group). Treatment with dual GIP/GLP-2 analogues was initiated 4 weeks later for 8 weeks. At the organ level, GL-0001 modified biomechanical parameters by increasing ultimate load, postyield displacement, and energy-to-fracture of cortical bone. GL-0001 also prevented excess trabecular bone degradation at the appendicular skeleton and enhanced bone ECM material properties in cortical bone through a reduction of the mineral-to-matrix ratio and augmentation in enzymatic collagen cross-linking. These results demonstrate that targeting bone ECM material properties is a viable option to enhance bone strength and opens an innovative pathway for the treatment of patients suffering from bone fragility. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). Abstract The first-in-class unimolecular dual GIP/GLP-2 analogue GL-0001 activates both GIPr and GLP-2r, resulting in cAMP production and lysyl oxidase expression. Then lysyl oxidase increases collagen cross-linking and bone material strength.

• 2

  Efficacy of targeting bone-specific GIP receptor in ovariectomy-induced bone loss

  The Journal of endocrinology · 2018

  📚 18 citations🔓 Open Access📄 PDF gratuit ↗

  Lire l'abstract Crossref ↓

  Glucose-dependent insulinotropic polypeptide (GIP) has been recognized in the last decade as an important contributor of bone remodelling and is necessary for optimal bone quality. However, GIP receptors are expressed in several tissues in the body and little is known about the direct vs indirect effects of GIP on bone remodelling and quality. The aims of the present study were to validate two new GIP analogues, called [d-Ala2]-GIP-Tag and [d-Ala2]-GIP1–30, which specifically target either bone or whole-body GIP receptors, respectively; and to ascertain the beneficial effects of GIP therapy on bone in a mouse model of ovariectomy-induced bone loss. Both GIP analogues exhibited similar binding capacities at the GIP receptor and intracellular responses as full-length GIP1–42. Furthermore, only [d-Ala2]-GIP-Tag, but not [d-Ala2]-GIP1–30, was undoubtedly found exclusively in the bone matrix and released at acidic pH. In ovariectomized animals, [d-Ala2]-GIP1–30but not [d-Ala2]-GIP-Tag ameliorated bone stiffness at the same magnitude than alendronate treatment. Only [d-Ala2]-GIP1–30treatment led to significant ameliorations in cortical microarchitecture. Although alendronate treatment increased the hardness of the bone matrix and the type B carbonate substitution in the hydroxyapatite crystals, none of the GIP analogues modified bone matrix composition. Interestingly, in ovariectomy-induced bone loss, [d-Ala2]-GIP-Tag failed to alter bone strength, microarchitecture and bone matrix composition. Overall, this study shows that the use of a GIP analogue that target whole-body GIP receptors might be useful to improve bone strength in ovariectomized animals.

• 3

  Enteroendocrine K Cells Exert Complementary Effects to Control Bone Quality and Mass in Mice

  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020

  📚 16 citations🔓 Open Access📄 PDF gratuit ↗

  Lire l'abstract Crossref ↓

  ABSTRACT The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K cells (GIP-DT) was investigated. Mice deficient in GIP secretion exhibited lower bone strength, trabecular bone mass, trabecular number, and cortical thickness, notably due to higher bone resorption. Alterations of microstructure, modifications of bone compositional parameters, represented by lower collagen cross-linking, were also apparent. None of these alterations were observed in GIP-DT mice lacking enteroendocrine K cells, suggesting that another K-cell secretory product acts to counteract GIP action. To assess this, stable analogues of the known K-cell peptide hormones, xenin and GIP, were administered to mature NIH Swiss male mice. Both were capable of modulating bone strength mostly by altering bone microstructure, bone gene expression, and bone compositional parameters. However, the two molecules exhibited opposite actions on bone physiology, with evidence that xenin effects are mediated indirectly, possibly via neural networks. Our data highlight a previously unknown interaction between GIP and xenin, which both moderate gut-bone connectivity. © 2020 American Society for Bone and Mineral Research.

Publications scientifiques (6) — classées par pathologie

Source PubMed · Recherche par auteur (homonymes possibles, vérifier l'affiliation).

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