Browsing by Author "Ford Versypt, Ashlee N."

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    Bifurcation study of blood flow control in the kidney.
    (Elsevier, 2015-05) Ford Versypt, Ashlee N.; Makrides, Elizabeth; Arciero, Julia C.; Ellwein, Laura; Layton, Anita T.; Department of Mathematical Sciences, School of Science
    Renal blood flow is maintained within a narrow window by a set of intrinsic autoregulatory mechanisms. Here, a mathematical model of renal hemodynamics control in the rat kidney is used to understand the interactions between two major renal autoregulatory mechanisms: the myogenic response and tubuloglomerular feedback. A bifurcation analysis of the model equations is performed to assess the effects of the delay and sensitivity of the feedback system and the time constants governing the response of vessel diameter and smooth muscle tone. The results of the bifurcation analysis are verified using numerical simulations of the full nonlinear model. Both the analytical and numerical results predict the generation of limit cycle oscillations under certain physiologically relevant conditions, as observed in vivo.
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    Fructooligosaccharides act on the gut-bone axis to improve bone independent of Tregs and alter osteocytes in young adult C57BL/6 female mice
    (Oxford University Press, 2024-02-21) Islam, Proapa; Ice, John A.; Alake, Sanmi E.; Adedigba, Pelumi; Hatter, Bethany; Robinson, Kara; Clarke, Stephen L.; Ford Versypt, Ashlee N.; Ritchey, Jerry; Lucas, Edralin A.; Smith, Brenda J.; Obstetrics and Gynecology, School of Medicine
    Targeting the gut-bone axis with probiotics and prebiotics is considered as a promising strategy to reduce the risk of osteoporosis. Gut-derived short chain fatty acids (SCFA) mediate the effects of probiotics on bone via Tregs, but it is not known whether prebiotics act through a similar mechanism. We investigated how 2 different prebiotics, tart cherry (TC) and fructooligosaccharide (FOS), affect bone, and whether Tregs are required for this response. Eight-wk-old C57BL/6 female mice were fed with diets supplemented with 10% w/w TC, FOS, or a control diet (Con; AIN-93M) diet, and they received an isotype control or CD25 Ab to suppress Tregs. The FOS diet increased BMC, density, and trabecular bone volume in the vertebra (~40%) and proximal tibia (~30%) compared to the TC and control diets (Con), irrespective of CD25 treatment. Both prebiotics increased (P < .01) fecal SCFAs, but the response was greater with FOS. To determine how FOS affected bone cells, we examined genes involved in osteoblast and osteoclast differentiation and activity as well as genes expressed by osteocytes. The FOS increased the expression of regulators of osteoblast differentiation (bone morphogenetic protein 2 [Bmp2], Wnt family member 10b [Wnt10b] and Osterix [Osx]) and type 1 collagen). Osteoclasts regulators were unaltered. The FOS also increased the expression of genes associated with osteocytes, including (Phex), matrix extracellular phosphoglycoprotein (Mepe), and dentin matrix acidic phosphoprotein 1 (Dmp-1). However, Sost, the gene that encodes for sclerostin was also increased by FOS as the number and density of osteocytes increased. These findings demonstrate that FOS has a greater effect on the bone mass and structure in young adult female mice than TC and that its influence on osteoblasts and osteocytes is not dependent on Tregs.
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    Mathematical modeling of the effects of Wnt-10b on bone metabolism
    (Wiley, 2022) Cook, Carley V.; Islam, Mohammad Aminul; Smith, Brenda J.; Ford Versypt, Ashlee N.; Obstetrics and Gynecology, School of Medicine
    Bone health is determined by factors including bone metabolism or remodeling. Wnt-10b alters osteoblastogenesis through pre-osteoblast proliferation and differentiation and osteoblast apoptosis rate, which collectively lead to the increase of bone density. To model this, we adapted a previously published model of bone remodeling. The resulting model for the bone compartment includes differential equations for active osteoclasts, pre-osteoblasts, osteoblasts, osteocytes, and the amount of bone present at the remodeling site. Our alterations to the original model consist of extending it past a single remodeling cycle and implementing a direct relationship to Wnt-10b. Four new parameters were estimated and validated using normalized data from mice. The model connects Wnt-10b to bone metabolism and predicts the change in trabecular bone volume caused by a change in Wnt-10b input. We find that this model predicts the expected increase in pre-osteoblasts and osteoblasts while also pointing to a decrease in osteoclasts when Wnt-10b is increased.
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    Mathematical Modeling of the Gut–Bone Axis and Implications of Butyrate Treatment on Osteoimmunology
    (American Chemical Society, 2021) Islam, Mohammad Aminul; Cook, Carley V.; Smith, Brenda J.; Ford Versypt, Ashlee N.; Obstetrics and Gynecology, School of Medicine
    Butyrate, a short-chain fatty acid produced by the gut microbiota, has pivotal roles in the regulation of the immune system. Recent studies have revealed that butyrate increases the differentiation of peripheral regulatory T cells in the gut-bone axis and promotes osteoblasts' bone forming activity. However, the mechanism of the therapeutic benefit of butyrate in bone remodeling remains incompletely understood. Here, we develop a multicompartment mathematical model to quantitatively predict the contribution of butyrate on the expansion of regulatory T cells in the gut, blood, and bone compartments. We investigate the interplay between regulatory T cell-derived TGF-β and CD8+ T cell-derived Wnt-10b with changes in gut butyrate concentration. In addition, we connect our model to a detailed model of bone metabolism to study the impacts of butyrate and Wnt-10b on trabecular bone volume. Our results indicate both direct and indirect immune-mediated impacts of butyrate on bone metabolism.