PMID- 26427607
OWN - NLM
STAT- MEDLINE
DCOM- 20160825
LR  - 20151121
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 24
IP  - 24
DP  - 2015 Dec 15
TI  - Impaired bone remodeling and its correction by combination therapy in a mouse 
      model of mucopolysaccharidosis-I.
PG  - 7075-86
LID - 10.1093/hmg/ddv407 [doi]
AB  - Mucopolysaccharidosis-I (MPS-I) is a lysosomal storage disease (LSD) caused by 
      inactivating mutations of IDUA, encoding the glycosaminoglycan-degrading enzyme 
      alpha-l-iduronidase. Although MPS-I is associated with skeletal abnormalities, the 
      impact of IDUA deficiency on bone remodeling is poorly defined. Here we report 
      that Idua-deficient mice progressively develop a high bone mass phenotype with 
      pathological lysosomal storage in cells of the osteoblast lineage. 
      Histomorphometric quantification identified shortening of bone-forming units and 
      reduced osteoclast numbers per bone surface. This phenotype was not transferable 
      into wild-type mice by bone marrow transplantation (BMT). In contrast, the high 
      bone mass phenotype of Idua-deficient mice was prevented by BMT from wild-type 
      donors. At the cellular level, BMT did not only normalize defects of 
      Idua-deficient osteoblasts and osteocytes but additionally caused increased 
      osteoclastogenesis. Based on clinical observations in an individual with MPS-I, 
      previously subjected to BMT and enzyme replacement therapy (ERT), we treated 
      Idua-deficient mice accordingly and found that combining both treatments 
      normalized all histomorphometric parameters of bone remodeling. Our results 
      demonstrate that BMT and ERT profoundly affect skeletal remodeling of 
      Idua-deficient mice, thereby suggesting that individuals with MPS-I should be 
      monitored for their bone remodeling status, before and after treatment, to avoid 
      long-term skeletal complications.
CI  - (c) The Author 2015. Published by Oxford University Press. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Kuehn, Sonja C
AU  - Kuehn SC
AD  - Department of Osteology and Biomechanics.
FAU - Koehne, Till
AU  - Koehne T
AD  - Department of Osteology and Biomechanics, Department of Orthodontics.
FAU - Cornils, Kerstin
AU  - Cornils K
AD  - Department of Stem Cell Transplantation, Research Department Cell and Gene 
      Therapy.
FAU - Markmann, Sandra
AU  - Markmann S
AD  - Children's Hospital, Department of Biochemistry, and.
FAU - Riedel, Christoph
AU  - Riedel C
AD  - Department of Osteology and Biomechanics.
FAU - Pestka, Jan M
AU  - Pestka JM
AD  - Department of Osteology and Biomechanics.
FAU - Schweizer, Michaela
AU  - Schweizer M
AD  - Center of Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 
      Hamburg 20246, Germany and.
FAU - Baldauf, Christina
AU  - Baldauf C
AD  - Department of Osteology and Biomechanics.
FAU - Yorgan, Timur A
AU  - Yorgan TA
AD  - Department of Osteology and Biomechanics.
FAU - Krause, Matthias
AU  - Krause M
AD  - Department of Osteology and Biomechanics.
FAU - Keller, Johannes
AU  - Keller J
AD  - Department of Osteology and Biomechanics.
FAU - Neven, Mona
AU  - Neven M
AD  - Department of Osteology and Biomechanics.
FAU - Breyer, Sandra
AU  - Breyer S
AD  - Children's Hospital Hamburg-Altona, Department of Orthopedics, University Clinic 
      Hamburg, Hamburg 22763, Germany.
FAU - Stuecker, Ralf
AU  - Stuecker R
AD  - Children's Hospital Hamburg-Altona, Department of Orthopedics, University Clinic 
      Hamburg, Hamburg 22763, Germany.
FAU - Muschol, Nicole
AU  - Muschol N
AD  - Children's Hospital, Department of Biochemistry, and.
FAU - Busse, Bjoern
AU  - Busse B
AD  - Department of Osteology and Biomechanics.
FAU - Braulke, Thomas
AU  - Braulke T
AD  - Children's Hospital, Department of Biochemistry, and.
FAU - Fehse, Boris
AU  - Fehse B
AD  - Department of Stem Cell Transplantation, Research Department Cell and Gene 
      Therapy.
FAU - Amling, Michael
AU  - Amling M
AD  - Department of Osteology and Biomechanics.
FAU - Schinke, Thorsten
AU  - Schinke T
AD  - Department of Osteology and Biomechanics, schinke@uke.de.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151001
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - EC 3.2.1.76 (Iduronidase)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation
MH  - *Bone Remodeling
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Child
MH  - Combined Modality Therapy
MH  - Disease Models, Animal
MH  - Enzyme Replacement Therapy
MH  - Female
MH  - Humans
MH  - Iduronidase/deficiency/genetics/*therapeutic use
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mucopolysaccharidosis I/pathology/*physiopathology/*therapy
MH  - Osteoclasts/enzymology
EDAT- 2015/10/03 06:00
MHDA- 2016/08/26 06:00
CRDT- 2015/10/03 06:00
PHST- 2015/07/13 00:00 [received]
PHST- 2015/09/22 00:00 [accepted]
PHST- 2015/10/03 06:00 [entrez]
PHST- 2015/10/03 06:00 [pubmed]
PHST- 2016/08/26 06:00 [medline]
AID - ddv407 [pii]
AID - 10.1093/hmg/ddv407 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2015 Dec 15;24(24):7075-86. doi: 10.1093/hmg/ddv407. Epub 2015 Oct 
      1.