"Iron induced cell proliferation and synovitis by 8-fold."
"Changes induced by IRON in the blood may be the BASIS of the increase
in cell proliferation and the development of hemophilic synovitis "
Blood. 2004 Jun 1 [Epub ahead of print] Related Articles, Links
Pathobiology of hemophilic synovitis I: Over-expression of mdm2
oncogene.
Hakobyan N, Kazarian T, Jabbar AA, Jabbar KJ, Valentino LA.
Pediatrics- Hematology/Oncology, Rush University Medical Center,
Chicago, IL,
USA; Immunology/Microbiology, Rush University, Chicago, IL, USA.
Hemophilia is a genetic disease due to the deficiency of blood
coagulation factor VIII or IX.
Bleeding into joints is the most frequent manifestation of
hemophilia.
Hemarthrosis results in an inflammatory and proliferative disorder
termed hemophilic synovitis (HS).
In time, a debilitating, crippling arthritis, hemophilic arthropathy
develops.
Although the clinical sequence of events from joint bleeding to
synovitis to arthropathy are well documented, the component(s) in
blood and the molecular changes responsible for hemophilic
synovitis are not known.
Iron has long been suspected to be the culprit but direct evidence has
been lacking.
Previously, we showed that iron increased human synovial cell
proliferation and induced c-myc expression.
Here we show that bleeding into a joint in vivo and iron in vitro
result in increased expression of the p53-binding protein, mdm2. Iron
induced the expression of mdm2 by normal human synovial cells
approximately 8-fold.
In a murine model of human hemophilia A, hemarthrosis resulted in
pathological changes observed in human hemophilic synovitis and a
marked increase in synovial cell proliferation.
Iron, in vitro, induced the expression of mdm2.
These molecular changes induced by iron in the blood may be the basis
of the increase in cell proliferation and the development of
hemophilic synovitis.
PMID: 15172967 [PubMed - as supplied by publisher]
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Juvenile Rheumatoid Arthritis
INCREASED destruction by introduction of iron .
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EXPERIMENTAL BIOLOGY UPDATE:
Arthritic kids' iron supplements may hasten joint deterioration
By Diana Swift
WWASHINGTON, D.C. -
The iron supplements that many arthritic children take to combat
concomitant anemia may be hastening the deterioration of their joints,
Houston researchers say.
Led by biologist Roman Shypailo of the Children's Nutrition Research
Centre at Baylor College of Medicine, a Texas team looked at eight
children being treated for juvenile rheumatoid arthritis.
The patients, aged five to 15 years, received an intravenous
radioactive tracer dose of iron (0.03 microsievert).
Iron activity in affected joints was monitored on a position/energy-
sensitive gamma counter, while a second machine monitored whole-body
iron retention.
Iron deposition was measured two hours post-infusion and again at days
seven, 14, 28 and 56.
Anemic
"We found that iron excessively accumulates in arthritic joints and
probably contributes to the chronic damage," said Shypailo.
"That puts you between a rock and a hard place because many of these
arthritic kids are anemic and need iron supplements, which may worsen
the disease."
The study found a high level of agreement between the joint data and
the whole-body data, with a greater than 90% retention rate of the
infused iron both in joints and systemically.
Furthermore, six of eight patients showed increased uptake at the
affected joints: 165% over the first 30 days compared with initial
uptake at two hours.
The next step, he says, is to see if there is excessive deposition of
dietary iron in arthritic joints.
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Dietary Iron In Arthritic Joints 
Linear Mode
