Osteoporosis, a major public health problem, likely has its origins in childhood. During periods of rapid skeletal growth, diet may influence accrual of bone mineral density (BMD) and adult bone health. This study used novel approaches in bone imaging to further characterize optimal skeletal development and enhance our understanding of key dietary components that influence attainment of peak bone mass (PBM) and contribute to determinants of peak bone strength in peri-pubertal females. The use of a validated food-frequency questionnaire (FFQ) enabled the influence of usual dietary intake on bone parameters to be examined.This study examined the relationship of dietary intake of micronutrients and bone macro-architectural structure in peri-pubertal girls. This study suggested that vitamin C and zinc intake are associated with objective measures of bone status in 4th, but not 6th grade girls. This indicates potential differences in micronutrient and bone associations at various age-associated stages of bone maturation.The impact of dietary fat on peri-pubertal skeletal growth is not well characterized. This study examined relationships of select dietary fatty acid (FA) intakes and measures of bone status in peri-pubertal girls. This study suggested that MUFA, total PUFA, n-6 and linoleic acid (LA) are inversely associated with bone status prior to menarche, but composition of dietary fat may be more important during the early-pubertal years. Decreased intakes of n-6 PUFA may benefit bone health in young girls.The impact of a dietary protein on volumetric bone mineral density (vBMD), bone mineral content (BMC) and bone strength throughout maturation remains controversial. Given evidence of both anabolic and catabolic affects of protein on bone health, this study examined relations of dietary protein from different sources with bone parameters in peri-pubertal girls. This study showed that dietary protein intake is related to higher trabecular but not cortical vBMD, BMC and BSI, and accounts for 2-4% of their variability in peri-pubertal girls. The relationship seems to vary by the source of dietary protein and calcium intake. However, a negative impact of animal protein on bone health is not supported. Large scale observational and intervention studies are needed to establish causality.

Les facteurs de transcription Pitx ont été impliqués dans la croissance et la détermination de l’identité des membres postérieurs. D’abord, l’inactivation de Pitx1 chez la souris résulte en la transformation partielle des membres postérieurs en membres antérieurs. Ensuite, la double mutation de Pitx1 et de Pitx2 a montré l’activité redondante de ces facteurs pour la croissance des membres postérieurs. Ainsi, les souris mutantes Pitx1-/-;Pitx2néo/néo montrent une perte des éléments squelettiques proximaux et antérieurs. Des travaux récents ont impliqué les gènes de la famille des Iroquois dans le développement des membres. Tout particulièrement, les souris Irx3-/-;Irx5-/- montrent la perte des éléments squelettiques proximaux et antérieurs, exclusivement au niveau des membres postérieurs. Cette phénocopie entre les souris mutantes pour Pitx1/2 et Irx3/5 nous a amenés à poser trois hypothèses : (1) les Pitx sont responsables de l’expression de Irx dans les bourgeons postérieurs ; (2) à l’inverse, les Irx dirigent l’expression des Pitx ; (3) les Pitx et les Irx participent ensemble au programme génétique de croissance des bourgeons postérieurs. Nous avons pu conclure que les Pitx et les Irx font partie de cascades de régulation indépendantes l’une de l’autre et qu’ils sont capables d’interaction transcriptionnelle autant sur un promoteur générique que sur des régions conservées du locus de Tbx4. Enfin, autant l’inactivation Pitx que celle des Irx mène à un retard d’expression de Pax9 exclusivement dans les bourgeons postérieurs. Ainsi, les Pitx et les Irx semblent agir sur des programmes génétiques parallèles impliqués dans la croissance et le patterning des membres postérieurs. / The Pitx transcription factors have been implicated in growth and specification of hindlimb identity. First, Pitx1 gene inactivation in mice results in partial transformation of hindlimbs into forelimbs. Further, Pitx1 and Pitx2 have redundant activity for hindlimb growth as demonstrated in double mutant mice for Pitx1 and Pitx2. Indeed, Pitx1-/-;Pitx2neo/neo mice show loss of proximal (femur) and anterior (ilium, tibia and first digit) skeletal structures. A collaborator, Dr C. C. Hui of Toronto University, has demonstrated the importance of the Iroquois (Irx) family transcription factors in hindlimb development. Irx3-/-;Irx5-/- mice show loss of proximal and anterior skeletal structures, exclusively in hindlimbs, even if Irx are expressed in the two limb pairs. This phenocopy between Pitx and Irx mutants led us to investigate the interaction between these transcription factors with three hypotheses : (1) Pitx control Irx expression in hindlimb buds ; (2) the Irx direct Pitx gene expression in hindlimb bud ; (3) Pitx and Irx participate together in a growth regulation cascade in hindlimb buds. Our analyses led us to conclude that Pitx and Irx are in independant genetic cascade in hindlimb buds. However, we observed that Pitx and Irx transcription factors are capable of transcriptionnal interactions assessed using either a generic promoter or conserved regions of the Tbx4 locus. Finally, inactivation of either Pitx or Irx led to a delay of Pax9 expression exclusively in hindlimb buds. In sum, Pitx and Irx gene appear to act on parallel genetic programs involved in control of hindlimbs growth and patterning.

No description available.

<p> Down syndrome (DS) is a complex genetic disorder caused by the triplication of human chromosome 21 (Hsa21). The presence of an extra copy of an entire chromosome greatly disrupts the copy number and expression of over 350 protein coding genes. This gene dosage imbalance has far-reaching effects on normal development and aging, leading to cognitive and skeletal defects that emerge earlier in life than the general population.</p> <p> The present study begins by characterizing skeletal development in young male Ts65Dn mice to test the hypothesis that skeletal defects in male Ts65Dn mice are developmental in nature.Femurs from young mice ranging from postnatal day 12- to 42-days of age (P12-42) were measured and analyzed by microcomputed tomography (μCT). Cortical defects were present generally throughout development, but trabecular defects emerged at P30 and persisted until P42. </p> <p> The gene <i>Dual-specificity tyrosine-regulated kinase 1a </i>(<i>Dyrk1a</i>) is triplicated in both DS and in Ts65Dn mice and has been implicated as a putative cause of both cognitive and skeletal defects. To test the hypothesis that trisomic <i>Dyrk1a</i> is related to the emergence of trabecular defects at P30, expression of <i>Dyrk1a</i> in the femurs of male Ts65Dn mice was quantified by qPCR. Expression was shown to fluctuate throughout development and overexpression generally aligned with the emergence of trabecular defects at P30.</p> <p> The growth rate in trabecular measures between male Ts65Dn and euploid littermates was similar between P30 and P42, suggesting a closer look into cellular mechanisms at P42. Assessment of proliferation of BMSCs, differentiation and activity of osteoblasts showed no significant differences between Ts65Dn and euploid cellular activity, suggesting that the cellular microenvironment has a greater influence on cellular activity than genetic background.</p> These data led to the hypothesis that reduction of <i>Dyrk1a</i> gene expression and pharmacological inhibition of DYRK1A could be executed during a critical period to prevent the emergence of trabecular defects at P30. To tests this hypothesis, doxycycline-induced cre-lox recombination to reduce <i>Dyrk1a</i> gene copy number or the DYRK1A inhibitor CX-4945 began at P21. The results of both genetic and pharmacological interventions suggest that trisomic <i>Dyrk1a</i> does not influence the emergence of trabecular defects up to P30. Instead, data suggest that the critical window for the rescue of trabecular defects lies between P30 and P42.