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Dense iron deposits within the siderosome / arthritis
Dense iron deposits within the siderosome / arthritis -- Posted by ironjustice@aol.com on 07-18-05 07:38
Annals of the Rheumatic Diseases 2005;64:816-823
=A9 2005 by BMJ Publishing Group Ltd & European League Against
Rheumatism
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EXTENDED REPORT
Increased expression of humanin peptide in diffuse-type pigmented
villonodular synovitis: implication of its mitochondrial abnormality
K Ijiri1,2, H Tsuruga3, H Sakakima1, K Tomita5, N Taniguchi4, K
Shimoonoda4, S Komiya4, M B Goldring2, H J Majima5 and T Matsuyama3
1 Course of Physiotherapy, School of Health Science, Faculty of
Medicine, Kagoshima University, Kagoshima, Japan
2 Beth Israel Deaconess Medical Center, New England Baptist Bone and
Joint Institute, Boston, MA, USA
3 Immunology and Medical Zoology, Graduate School of Medicine,
Kagoshima University, Kagoshima, Japan
4 Department of Neuro-Musculoskeletal Disorder, Kagoshima University
Graduate School of Medicine and Dentistry, Kagoshima University,
Kagoshima, Japan
5 Department of Oncology, Kagoshima University Graduate School of
Medicine and Dental Science, Kagoshima, Japan
Correspondence to:
Dr K Ijiri
Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine,
Room 237, 4 Blackfan, Circle, Boston, MA 02115, USA;
kijiri@bidmc.harvard.edu
Objectives: To define the pathogenesis of pigmented villonodular
synovitis (PVNS), by searching for highly expressed genes in primary
synovial cells from patients with PVNS.
Methods: A combination of subtraction cloning and Southern colony
hybridisation was used to detect highly expressed genes in PVNS in
comparison with rheumatoid synovial cells. Northern hybridisation was
performed to confirm the differential expression of the humanin gene in
PVNS. Expression of the humanin peptide was analysed by western
blotting and immunohistochemistry. Electron microscopic
immunohistochemistry was performed to investigate the distribution of
this peptide within the cell.
Results: 68 highly expressed genes were identified in PVNS. Humanin
genes were strongly expressed in diffuse-type PVNS, but were barely
detected in nodular-type PVNS, rheumatoid arthritis, or osteoarthritis.
Humanin peptide was identified in synovium from diffuse-type PVNS, and
most of the positive cells were distributed in the deep layer of the
synovial tissue. Double staining with anti-humanin and anti-heat shock
protein 60 showed that humanin was expressed mainly in mitochondria.
Electron microscopy disclosed immunolocalisation of this peptide,
predominantly around dense iron deposits within the siderosome.
Conclusions: Increased expression of the humanin peptide in
mitochondria and siderosomes is characteristic of synovial cells from
diffuse-type PVNS. Humanin is an anti-apoptotic peptide which is
encoded in the mitochondrial genome. Present findings suggest that
mitochondrial dysfunction may be the principal factor in pathogenesis
of diffuse-type PVNS and that humanin peptide may play a part in the
neoplastic process in this form of PVNS.
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Abbreviations: BSA, bovine serum albumin; GAPDH,
glyceraldehyde-3-phosphate dehydrogenase; hsp, heat shock protein;
IMDM, Iscove modified Dulbecco's medium; OA, osteoarthritis; PBS,
phosphate buffered saline; PCR, polymerase chain reaction; PVNS,
pigmented villonodular synovitis; RA, rheumatoid arthritis; RT-PCR,
reverse transcriptase-polymerase chain reaction; SDS, sodium dodecyl
sulphate; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel
electrophoresis; SSC, saline sodium citrate
Keywords: humanin; mitochondria; pigmented villonodular synovitis
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