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@ARTICLE{Rauner:153710,
author = {M. Rauner and U. Baschant and A. Roetto and R. M.
Pellegrino and S. Rother and J. Salbach-Hirsch and H.
Weidner and V. Hintze and G. Campbell and A. Petzold and R.
Lemaitre and I. Henry and T. Bellido and I. Theurl and S.
Altamura and S. Colucci and M. U. Muckenthaler and G. Schett
and D. Komla Ebri and J. H. D. Bassett and G. R. Williams
and U. Platzbecker and L. C. Hofbauer$^*$},
title = {{T}ransferrin receptor 2 controls bone mass and
pathological bone formation via {BMP} and {W}nt signaling.},
journal = {Nature metabolism},
volume = {1},
number = {1},
issn = {2522-5812},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2020-00408},
pages = {111 - 124},
year = {2019},
abstract = {Transferrin receptor 2 (Tfr2) is mainly expressed in the
liver and controls iron homeostasis. Here, we identify Tfr2
as a regulator of bone homeostasis that inhibits bone
formation. Mice lacking Tfr2 display increased bone mass and
mineralization independent of iron homeostasis and hepatic
Tfr2. Bone marrow transplantation experiments and studies of
cell-specific Tfr2 knockout mice demonstrate that Tfr2
impairs BMP-p38MAPK signaling and decreases expression of
the Wnt inhibitor sclerostin specifically in osteoblasts.
Reactivation of MAPK or overexpression of sclerostin rescues
skeletal abnormalities in Tfr2 knockout mice. We further
show that the extracellular domain of Tfr2 binds BMPs and
inhibits BMP-2-induced heterotopic ossification by acting as
a decoy receptor. These data indicate that Tfr2 limits bone
formation by modulating BMP signaling, possibly through
direct interaction with BMP either as a receptor or as a
co-receptor in a complex with other BMP receptors. Finally,
the Tfr2 extracellular domain may be effective in the
treatment of conditions associated with pathological bone
formation.},
cin = {L301},
ddc = {610},
cid = {I:(DE-He78)L301-20160331},
pnm = {899 - ohne Topic (POF3-899)},
pid = {G:(DE-HGF)POF3-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30886999},
pmc = {pmc:PMC6420074},
doi = {10.1038/s42255-018-0005-8},
url = {https://inrepo02.dkfz.de/record/153710},
}