Cytokine accumulation in osteitis fibrosa of renal osteodystrophy

Abstract

Bone marrow fibrosis occurs in association with a number of pathological states. Despite the extensive fibrosis that sometimes characterizes renal osteodystrophy, little is known about the factors that contribute to marrow accumulation of fibrous tissue. Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism. Bone sections were stained with antibodies to human interleukin1a (IL-1a), IL-6, IL-11, tumor necrosis factor-a (TNF-a) and transforming growth factor-ß (TGF-ß) using an undecalcified plastic embedding method. Intense staining for IL-1a, IL-6, TNF-a and TGF-ß was evident within the fibrotic tissue of the bone marrow while minimal IL-11 was detected. The extent of cytokine deposition corresponded to the severity of fibrosis, suggesting their possible involvement in the local regulation of the fibrotic response. Because immunoreactive TGF-ß and IL-6 were also detected in osteoblasts and osteocytes, we conclude that selective cytokine accumulation may have a role in modulating bone and marrow cell function in parathyroid-mediated uremic bone disease.

Anaemia in kidney disease: harnessing hypoxia responses for therapy

“…Bone marrow inflammatory cytokines are increased in patients with renal osteodystrophy 156,157 —a condition that is associated with erythropoietin resistance. A link between inflammation and decreased erythropoiesis was demonstrated by relatively decreased levels of serum erythropoietin in anaemic patients without renal failure who had inflammation caused by autoimmune disease 158 or malignancies 159 as opposed to levels in similarly anaemic patients without inflammation.…”

Dietary‐Induced Hyperparathyroidism Affects Serum and Gingival Proinflammatory Cytokine Levels in Rats

“…IL‐1β and TNF‐α concentrations in the gingival homogenates were increased in dHPT, with the highest amounts in rats with dHPT + periodontitis; again, positive correlations were noted between PTH and the gingival cytokines in dHPT. Immunohistochemistry demonstrated that IL‐1β and TNF‐α levels were elevated in the iliac bone biopsies of patients with secondary HPT due to chronic renal diseases 32,47 . Secondary HPT may also cause excessive accumulation of these cytokines in the endothelial tissues of patients with end‐stage renal failure, which promotes atherosclerotic alterations in the patients 48‐51 .…”

TGF-Beta Signaling in Bone with Chronic Kidney Disease

“…They concluded that the pathological condition of ROD may stimulate overproduction of TGF-β in patients undergoing hemodialysis. Using immunohistochemistry, Duarte et al [81] also demonstrated intense TGF-β expression in bone samples with osteitis fibrosa from patients with ROD, which is accompanied by extremely high bone turnover. A study conducted by Santos et al [82] indicated that TGF-β expression in bone changes before and after parathyroidectomy.…”

“…They also presented that activation of Runx2 or TCF-4 coenhances TCF and Runx2 activity and increases TGF-β receptor I expression [86]. As described above, high TGF-β protein expression has been observed in high-turnover bones from patients with end-stage renal disease [81,82]. Existence of a positive regulatory loop between TGF-β and Wnt signaling may lead to the pathogenesis of high-turnover bone disease in CKD.…”