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@ARTICLE{Linz:127020,
author = {A. Linz and Y. Knieper and T. Gronau and U. Hansen and A.
Aszodi and N. Garbi and G. Hämmerling$^*$ and T. Pap and P.
Bruckner and R. Dreier},
title = {{ER} {S}tress {D}uring the {P}ubertal {G}rowth {S}purt
{R}esults in {I}mpaired {L}ong-{B}one {G}rowth in
{C}hondrocyte-{S}pecific {ER}p57 {K}nockout {M}ice.},
journal = {Journal of bone and mineral research},
volume = {30},
number = {8},
issn = {0884-0431},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DKFZ-2017-03046},
pages = {1481 - 1493},
year = {2015},
abstract = {Long-bone growth by endochondral ossification is
cooperatively accomplished by chondrocyte proliferation,
hypertrophic differentiation, and appropriate secretion of
collagens, glycoproteins, and proteoglycans into the
extracellular matrix (ECM). Before folding and entering the
secretory pathway, ECM macromolecules in general are subject
to extensive posttranslational modification, orchestrated by
chaperone complexes in the endoplasmic reticulum (ER). ERp57
is a member of the protein disulfide isomerase (PDI) family
and facilitates correct folding of newly synthesized
glycoproteins by rearrangement of native disulfide bonds.
Here, we show that ERp57-dependent PDI activity is essential
for postnatal skeletal growth, especially during the
pubertal growth spurt characterized by intensive matrix
deposition. Loss of ERp57 in growth plates of
cartilage-specific ERp57 knockout mice (ERp57 KO) results in
ER stress, unfolded protein response (UPR), reduced
proliferation, and accelerated apoptotic cell death of
chondrocytes. Together this results in a delay of long-bone
growth with the following characteristics: (1) enlarged
growth plates; (2) expanded hypertrophic zones; (3) retarded
osteoclast recruitment; (4) delayed remodeling of the
proteoglycan-rich matrix; and (5) reduced numbers of bone
trabeculae. All the growth plate and bone abnormalities,
however, become attenuated after the pubertal growth spurt,
when protein synthesis is decelerated and, hence, ERp57
function is less essential.},
keywords = {Pdia3 protein, mouse (NLM Chemicals) / Protein
Disulfide-Isomerases (NLM Chemicals)},
cin = {D050},
ddc = {610},
cid = {I:(DE-He78)D050-20160331},
pnm = {314 - Tumor immunology (POF3-314)},
pid = {G:(DE-HGF)POF3-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25704664},
doi = {10.1002/jbmr.2484},
url = {https://inrepo02.dkfz.de/record/127020},
}