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La sialoprotéine osseuse dans le développement osseux, l'ostéogenèse et l'angiogenèse : régulations croisées avec l'ostéopontine

Abstract : The Small Integrin Binding Ligand N-Linked Glycoproteins family is involved in bone formation and angiogenesis, and it includes bone sialoprotein (BSP) and osteopontin (OPN). Our laboratory has characterized the phenotype of BSP-/- mice, which have a hypomineralised skeleton and are smaller presenting shorter long bone in adulthood. The analysis of their development has been complicated by a behavioral disorder of female BSP-/-, which do not form a nest after parturition. We performed a series of crossfoster breedings, which established that the bone phenotype of BSP-/- is of purely genetic origin. After birth, BSP-/- pups showed higher circulating level of OPN, which suggests a compensation of the lack of BSP by OPN. We developed a model of intermittent injection of PTH over the periosteum of the right mouse hemicalvaria to test the latter hypothesis. PTH induced a local increase of histological microtomographic and molecular bone formation parameters in both genotypes. The Inhibition of this protein by injection of siRNA did not change the anabolic effect of PTH in wild mice, in contrast, this anabolic effect was blocked in BSP-/- mice. These results suggest that OPN could replace BSP in some of its functions. Knowing that OPN is overexpressed in the absence of BSP and is highly angiogenic, we used a model of bone marrow ablation to analyze the revascularization of bone shaft. Three days after ablation BSP-/- femurs showed higher vessel density with higher expression of OPN and VEGF suggesting the involvement of one or both of these factors in the stimulation of angiogenesis. In conclusion, the absence of BSP affects the interplay between osteogenesis, angiogenesis
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Submitted on : Monday, October 27, 2014 - 2:29:20 PM
Last modification on : Thursday, November 21, 2019 - 2:29:28 AM
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Wafa Bouleftour. La sialoprotéine osseuse dans le développement osseux, l'ostéogenèse et l'angiogenèse : régulations croisées avec l'ostéopontine. Médecine humaine et pathologie. Université Jean Monnet - Saint-Etienne, 2013. Français. ⟨NNT : 2013STET017T⟩. ⟨tel-01077892⟩



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