TY  - JOUR
AU  - Linz, Andrea
AU  - Knieper, Yvonne
AU  - Gronau, Tobias
AU  - Hansen, Uwe
AU  - Aszodi, Attila
AU  - Garbi, Natalio
AU  - Hämmerling, Günter
AU  - Pap, Thomas
AU  - Bruckner, Peter
AU  - Dreier, Rita
TI  - ER Stress During the Pubertal Growth Spurt Results in Impaired Long-Bone Growth in Chondrocyte-Specific ERp57 Knockout Mice.
JO  - Journal of bone and mineral research
VL  - 30
IS  - 8
SN  - 0884-0431
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DKFZ-2017-03046
SP  - 1481 - 1493
PY  - 2015
AB  - 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.
KW  - Pdia3 protein, mouse (NLM Chemicals)
KW  - Protein Disulfide-Isomerases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25704664
DO  - DOI:10.1002/jbmr.2484
UR  - https://inrepo02.dkfz.de/record/127020
ER  -