Expression of the H- and L-subunits of ferritin in bone marrow macrophages of patients with osteoarthritis

Abstract

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/ μm2; n= 7 versus 71.07; 58.56–86.26 counts/ μm2; 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/ μm2; n= 7 versus 104.23; 91.53–118.70 counts/ μm2; 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.

What Is the Utility of Biomarkers for Assessing the Pathophysiology of Hip Osteoarthritis? A Systematic Review

“…In three studies [19,22,37], uCTX-II levels were elevated in patients with hip OA 1.3 to 3.1 times that of the control group with associated effect size (d) of 2.2 to 3.7. Serum CRP level was elevated in patients with hip OA compared with control subjects in two studies (2.1-8.2 times greater than control levels, d 1.0-28.7) [11,21] while failing to demonstrate an effect in another study [27]. Thirteen other biomarkers demonstrated differences in levels between OA and control patients in a single study (with approximately 70% demonstrating large effect sizes).…”

“…A total of 16 different biomarkers demonstrated differences between patients with hip OA and non-OA control subjects (Table 2) Although most biomarkers were assessed in only one ''diagnosis'' study, urinary level of type II collagen telopeptide (uCTX-II) [19,22,37] and serum C-reactive protein (CRP) [11,21,27] levels both were increased in patients with hip OA in more than one study. In three studies [19,22,37], uCTX-II levels were elevated in patients with hip OA 1.3 to 3.1 times that of the control group with associated effect size (d) of 2.2 to 3.7.…”

Neuroimmune expression in hip osteoarthritis: a systematic review

“…A local response on cartilage and bone was also observed when analyzing TGF-ß family cytokines. TGF-ß is an inductor of chondrocyte anabolic response and is antagonized by IL-1, that acts as a stimulator of cartilage degradation [ 18 , 32 ]. Accordingly, both TGF-ß1, − ß2 and -ß3 and IL-1 isoforms were found increased in these tissues.…”

Changes in chondrocyte gene expression following in vitro impaction of porcine articular cartilage in an impact injury model

“…Previously ferritin was up‐regulated in response to rheumatoid arthritis47 and inflammatory stimuli in general 48, 49. It recently was examined in macrophages of patients with OA and both the heavy and light subunits had higher expression in OA patients than in controls46 and we found ftl to be marginally up‐regulated in impacted samples. Chi3l1 expression levels were correlated with the degree of joint inflammation in rheumatoid arthritis patients50 and have been linked to the biological stress response of articular cartilage 51.…”

“…In studies completed by others, clu was up‐regulated in response to oxidative, mechanical and thermal stress 45. Ferritin (formed from its subunits fth1 and ftl) is a regulator of iron availability and excess iron has been implicated in OA progression, due to its role in the production of reactive oxygen species 46. Previously ferritin was up‐regulated in response to rheumatoid arthritis47 and inflammatory stimuli in general 48, 49.…”