Nancy Karam
PhD thesis, Université de Montréal, 2015 (degree/title-page year). Original French title: Rôle du facteur de transcription PITX1 dans les pathogenèses de l'ostéoporose et des maladies parodontales.
https://doi.org/10.71781/30087
Les titres, résumés et légendes des publications sont présentés en anglais.
Osteoporosis is a progressive bone disease that is char acterized by a decrease in bone mass and density leading to an increase d risk of fracture. Several studies have linked osteoporosis to the lo w bone density of the mandibles , the periodontal attachment loss, increasing of the alveolar crest heigh and tooth loss. This study aims to understand the mech anisms underlying bone loss. During mouse development, PITX1 plays a key role in th e identity of the hindlimb and the proper development of the jaws and teeth. Intere stingly, PITX1-null mice displayed severe skeletal phenotype. Whereas, ageing PITX1+ /- progressively deve loped OA-like lesions in cartilage associated with a drastic increas e in cortical and trab ecular bone formation. Conversely, expression anal ysis of osteoblasts deri ved from monozygotic twins discordant for osteoporosis report ed an 8.6-fold up-regulation of Pitx1 expression in osteoblasts from osteoporotic twins when compared with healthy ones. Collectively, these data prompted us to investigate the role of PITX1 in normal and pathological bone metabolism. In this context, transgenic Col1α1-Pitx1 mice over-expressing Pitx1 specifically in bone tissue under the type-I collagen promoter (2.3kb fragment) were generated and phenotypically characterized. These data suggested that Pitx1 overexpression induces an osteoporosis like phenotype accompanied with oral bone loss, edentulousness, dental and periodontal problems. These results suggested that Pitx1 overexpression induces alteration of bone homeostasis via the inactivating of the the Wnt/ β-catenin canonical pathway. This hypothesis was supported by the fact that treatment with lithium chloride, a Wnt canonical activator, rescued the phenotype. Finally, this study establishe s a crucial role of PITX1 in the regulation of bone mass and a possible involvement in the deve loppement of osteoporos is and periodontal disease via the inactivation of the Wnt/β-catenin canonical pathway. Keywords: PITX1, Osteoblasts, Bone mass, Oste oporosis, Dental problems, periodontal diseases, Tooth loss, Wnt/β-catenin pathway, DKK1
Utilisation des équipements
Un Mach-1 de Biosyntech évaluait des fémurs et mandibules de souris transgéniques et témoins en flexion trois points. Les courbes force–déplacement servaient à calculer la rigidité et le travail jusqu’au point ultime; les essais fémoraux mesuraient aussi la force ultime.
Matériaux (1)
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Configurations de test (1)
