Expression of the H- and L-subunits of ferritin in bone marrow macrophages of patients with osteoarthritis.
Osteoarthritis is a disease characterized by an increase in the production of reactive oxygen species (ROS) in afflicted joints. Excess iron, due to its role in the production of ROS and crystal deposition in the joints, is implicated in the disease progression of osteoarthritis. Ferritin is a major regulator of the bioavailability of iron, and its functions are determined largely by the combination of H- and L-subunits present in its outer protein shell. The purpose of the study was to investigate the expression of the H- and L-subunits of ferritin in bone marrow macrophages of osteoarthritis patients. The cytokine profiles were assessed as cytokines play an important role in the expression of the ferritin subunits. The H-subunit of ferritin in the bone marrow macrophages was significantly higher (P value = 0.035) in the osteoarthritis patients compared with the controls (107.84; 69.25-167.94 counts/μm(2); n = 7 versus 71.07; 58.56-86.26 counts/μm(2); n = 19). A marginally significant increase (P value = 0.059) was shown for the expression of the L-subunit in the osteoarthritis patients compared with the controls (133.03; 104.04-170.10 counts/μm(2); n = 7 versus 104.23; 91.53-118.70 counts/μm(2); n = 19). The osteoarthritis and control groups had comparable C-reactive protein, as well as proinflammatory and anti-inflammatory cytokine concentrations. The major exception was for transforming growth factor-β (TGF-β), which was higher (P value = 0.014) in the plasma of the osteoarthritis patients (16.69; 13.09-21.28 ng/mL; n = 7 versus 8.60; 6.34-11.67 ng/mL; n = 19). Up-regulation of the ferritin subunits decreases the levels of bioavailable iron and provides protection against the unwarranted production of ROS and crystal deposition. A role for TGF-β in the up-regulation of the expression of the H-subunit, and possibly the L-subunit, of ferritin is postulated in osteoarthritis.
Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Private Bag x323, Arcadia, Pretoria 0007, South Africa. akoorts@medic.up.ac.za
Alida Maria
AM
Koorts
Peter Ferenc
PF
Levay
Alan Norman
AN
Hall
Christiaan Frederick
CF
van der Merwe
Petrus Johannes
PJ
Becker
Doron Johan Manuel
DJ
Frantzen
Margaretha
M
Viljoen
D001052:Apoferritins / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D015207:Osteoarthritis, Hip / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D002097:C-Reactive Protein; D001052:Apoferritins