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@PHDTHESIS{Dzhanaev:811509,
author = {Dzhanaev, Robert},
othercontributors = {Jahnen-Dechent, Wilhelm and Mottaghy, Felix},
title = {{R}ational design and production of recombinant {RANK}
ligand},
school = {Rheinisch-Westfälische Technische Hochschule Aachen},
type = {Dissertation},
address = {Aachen},
publisher = {RWTH Aachen University},
reportid = {RWTH-2021-01222},
pages = {1 Online-Ressource : Illustrationen, Diagramme},
year = {2020},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University 2021; Dissertation, Rheinisch-Westfälische
Technische Hochschule Aachen, 2020},
abstract = {Calcium metabolism is tightly regulated through the complex
interaction of several hormonal factors. The supersaturated
state of calcium phosphate in body liquids creates a direct
prerequisite for mineral precipitation, which is actively
prevented by a number of local and circulating inhibitors of
calcification. However, various pathological conditions can
tip the balance in favor of insoluble salt formation.
Ectopic calcification is the abnormal biomineralization of
soft tissues which resembles the physiologic process of
osteogenesis. Being exposed to high blood calcium levels,
the vasculature represents one of the primary regions
affected by extraosseous mineral precipitation.
Hydroxyapatite deposition in the arterial wall is associated
with an increased risk of cardiovascular events and
all-cause mortality. Cardiovascular calcification is an
irreversible process, and the definitive treatment is
largely limited to surgical intervention. As the only cells
capable of resorbing mineralized matrices, osteoclasts are
promising targets for the therapy of ectopic calcifications.
The differentiation and activation of osteoclasts depend
essentially upon the tumor necrosis factor superfamily
member RANKL. Alongside its receptor, RANK, and natural
antagonist, OPG, it plays a pivotal role in bone breakdown.
The limited availability and high cost of cytokines produced
in eukaryotic cells pose a significant impediment to the
investigation of osteoclast-mediated calcified tissue
resorption. The soluble form of the murine RANKL was
successfully expressed in a mammalian cell line and purified
for use in a cell culture. Osteoclast precursors were
isolated from the hind limb long bones of a C57BL/6 mouse
and were maintained in a growth medium. Osteoclastogenesis
was induced by the stimulation of the progenitor cells with
the newly produced RANKL. The biological activity of the
cytokine was proved in osteoclast formation and bone
resorption assays.},
cin = {532500-2},
ddc = {610},
cid = {$I:(DE-82)532500-2_20140620$},
pnm = {INTRICARE - International Network for Training on Risks of
vascular Intimal Calcification And roads to Regression of
cardiovascular diseasE (722609)},
pid = {G:(EU-Grant)722609},
typ = {PUB:(DE-HGF)11},
doi = {10.18154/RWTH-2021-01222},
url = {https://publications.rwth-aachen.de/record/811509},
}
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