PMID- 26403062
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20220330
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 24
IP  - 3
DP  - 2016 Mar
TI  - Iron overload in a murine model of hereditary hemochromatosis is associated with 
      accelerated progression of osteoarthritis under mechanical stress.
PG  - 494-502
LID - S1063-4584(15)01321-7 [pii]
LID - 10.1016/j.joca.2015.09.007 [doi]
AB  - OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in 
      the Hfe gene characterised by systemic iron overload and associated with an 
      increased prevalence of osteoarthritis (OA) but the role of iron overload in the 
      development of OA is still undefined. To further understand the molecular 
      mechanisms involved we have used a murine model of HH and studied the progression 
      of experimental OA under mechanical stress. DESIGN: OA was surgically induced in 
      the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA 
      progression was assessed using histology, micro CT, gene expression and 
      immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a 
      systemic iron overload and an increased iron accumulation in the knee synovial 
      membrane following surgery. The histological OA score was significantly higher in 
      the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia 
      revealed increased subchondral bone volume and increased trabecular thickness. 
      Gene expression and immunohistochemical analysis showed a significant increase in 
      the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice 
      compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was 
      associated with an accelerated development of OA in mice. Our findings suggest 
      that synovial iron overload has a definite role in the progression of HH-related 
      OA.
CI  - Copyright (c) 2015 Osteoarthritis Research Society International. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Camacho, A
AU  - Camacho A
AD  - Department of Orthopedics, Centro Hospitalar Lisboa Central, Lisboa, Portugal; 
      PhD Program in Medicine, NOVA Medical School, University Nova de Lisboa, Lisbon, 
      Portugal; Centre of Marine Sciences (CCMAR), University of Algarve, Faro, 
      Portugal. Electronic address: antonio.camacho@chlc.min-saude.pt.
FAU - Simao, M
AU  - Simao M
AD  - Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal; PhD 
      Program in Biomedical Sciences, University of Algarve, Faro, Portugal.
FAU - Ea, H-K
AU  - Ea HK
AD  - Inserm 1132, Hopital Lariboisiere, Paris, France; Universite Paris Diderot, UFR 
      medicale, Assistance Publique-Hopitaux de Paris, Hopital Lariboisiere, Federation 
      de Rhumatologie, Paris, France.
FAU - Cohen-Solal, M
AU  - Cohen-Solal M
AD  - Inserm 1132, Hopital Lariboisiere, Paris, France; Universite Paris Diderot, UFR 
      medicale, Assistance Publique-Hopitaux de Paris, Hopital Lariboisiere, Federation 
      de Rhumatologie, Paris, France.
FAU - Richette, P
AU  - Richette P
AD  - Inserm 1132, Hopital Lariboisiere, Paris, France; Universite Paris Diderot, UFR 
      medicale, Assistance Publique-Hopitaux de Paris, Hopital Lariboisiere, Federation 
      de Rhumatologie, Paris, France.
FAU - Branco, J
AU  - Branco J
AD  - Department of Rheumatology, Hospital Egas Moniz, Centro Hospitalar Lisboa 
      Ocidental EPE, Lisbon, Portugal; CEDOC - Chronic Diseases Research Center, NOVA 
      Medical School, University Nova de Lisboa, Lisbon, Portugal.
FAU - Cancela, M L
AU  - Cancela ML
AD  - Department of Biomedical Sciences and Medicine (DCBM), University of Algarve, 
      Faro, Portugal; Centre of Marine Sciences (CCMAR), University of Algarve, Faro, 
      Portugal.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150925
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Hemochromatosis Protein)
RN  - 0 (Hfe protein, mouse)
RN  - E1UOL152H7 (Iron)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Cartilage, Articular/pathology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Gene Expression Regulation/physiology
MH  - Hemochromatosis/*complications/genetics/metabolism
MH  - Hemochromatosis Protein
MH  - Iron/metabolism
MH  - Iron Overload/*complications/genetics/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Menisci, Tibial/surgery
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mutation
MH  - Osteoarthritis/*etiology/metabolism/pathology
MH  - Stress, Mechanical
MH  - Synovial Membrane/metabolism
OTO - NOTNLM
OT  - Hereditary hemochromatosis
OT  - Iron overload
OT  - Mechanical stress
OT  - Mouse model
OT  - Osteoarthritis
EDAT- 2015/09/26 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/09/26 06:00
PHST- 2015/06/08 00:00 [received]
PHST- 2015/08/21 00:00 [revised]
PHST- 2015/09/11 00:00 [accepted]
PHST- 2015/09/26 06:00 [entrez]
PHST- 2015/09/26 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - S1063-4584(15)01321-7 [pii]
AID - 10.1016/j.joca.2015.09.007 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2016 Mar;24(3):494-502. doi: 
      10.1016/j.joca.2015.09.007. Epub 2015 Sep 25.