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Endothelin-Converting Enzyme-1 Depen...
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Johnson, Michael G.
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Endothelin-Converting Enzyme-1 Dependent Endothelin 1 Signaling in Osteogenesis.
Record Type:
Electronic resources : Monograph/item
Title/Author:
Endothelin-Converting Enzyme-1 Dependent Endothelin 1 Signaling in Osteogenesis./
Author:
Johnson, Michael G.
Description:
107 p.
Notes:
Source: Dissertation Abstracts International, Volume: 77-05(E), Section: B.
Contained By:
Dissertation Abstracts International77-05B(E).
Subject:
Endocrinology. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3746011
ISBN:
9781339391281
Endothelin-Converting Enzyme-1 Dependent Endothelin 1 Signaling in Osteogenesis.
Johnson, Michael G.
Endothelin-Converting Enzyme-1 Dependent Endothelin 1 Signaling in Osteogenesis.
- 107 p.
Source: Dissertation Abstracts International, Volume: 77-05(E), Section: B.
Thesis (Ph.D.)--The University of Wisconsin - Madison, 2016.
Previously, we identified Ece1, encoding endothelin-converting-enzyme-1 (ECE1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We bred congenic mice to isolate the smallest possible DNA interval within Bmd7 that affects bone size and strength (3MB) and found that this interval, containing Ece1, affects bone size and strength. To test the hypothesis that endothelin 1 (ET1) signaling influences mineralization of osteoblasts, we exposed immortalized mouse osteoblast-like (TMOb) cells to big ET1 resulting in greater mineralization, increased RUNX2 and collagen production, increased secretion of IGF1 and decreased secretion of SOST and DKK1 than unexposed TMOb cells. Blockade of ET1 signaling in TMOb cells reduced mineralization and decreased IGF1 secretion and increased secretion of SOST and DKK1. In ex vivo bone organ culture on bovine and human trabecular bone cores, we determined the effect of exogenous big ET1 and EDNRA blockade on osteogenesis and response to mechanical load in whole tissue. Addition of exogenous big ET1 increased the percent change of elastic modulus (Eapp) relative to control. In human subjects, blockade of ET1 decreased Eapp in the female subject but not the male. We built Tamoxifen inducible and osteoblast lineage Ece1 conditional knockouts. We hypothesize that bones from Ece1 knockout mice will have smaller and weaker bones. Analysis of these bone is underway.
ISBN: 9781339391281Subjects--Topical Terms:
610914
Endocrinology.
Endothelin-Converting Enzyme-1 Dependent Endothelin 1 Signaling in Osteogenesis.
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107 p.
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Source: Dissertation Abstracts International, Volume: 77-05(E), Section: B.
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Adviser: Marc K. Drezner.
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Thesis (Ph.D.)--The University of Wisconsin - Madison, 2016.
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Previously, we identified Ece1, encoding endothelin-converting-enzyme-1 (ECE1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We bred congenic mice to isolate the smallest possible DNA interval within Bmd7 that affects bone size and strength (3MB) and found that this interval, containing Ece1, affects bone size and strength. To test the hypothesis that endothelin 1 (ET1) signaling influences mineralization of osteoblasts, we exposed immortalized mouse osteoblast-like (TMOb) cells to big ET1 resulting in greater mineralization, increased RUNX2 and collagen production, increased secretion of IGF1 and decreased secretion of SOST and DKK1 than unexposed TMOb cells. Blockade of ET1 signaling in TMOb cells reduced mineralization and decreased IGF1 secretion and increased secretion of SOST and DKK1. In ex vivo bone organ culture on bovine and human trabecular bone cores, we determined the effect of exogenous big ET1 and EDNRA blockade on osteogenesis and response to mechanical load in whole tissue. Addition of exogenous big ET1 increased the percent change of elastic modulus (Eapp) relative to control. In human subjects, blockade of ET1 decreased Eapp in the female subject but not the male. We built Tamoxifen inducible and osteoblast lineage Ece1 conditional knockouts. We hypothesize that bones from Ece1 knockout mice will have smaller and weaker bones. Analysis of these bone is underway.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3746011
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