Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy. (2nd June 2015)

• Record Type: Journal Article
• Authors: Petrova, Nina L.; Petrov, Peter K.; Edmonds, Michael E.; Shanahan, Catherine M.
• Other Names: Scaramuzza Andrea Academic Editor.
• Is Part Of: Journal of diabetes research. Volume 2015(2015)
• Publication Date: 2015-06-02
• Subjects: Diabetes -- Periodicals; Diabetes -- Pathophysiology -- Periodicals; Diabetes -- Prevention -- Periodicals; Diabetes -- Etiology -- Periodicals; Diabetes -- Epidemiology -- Periodicals; Diabetes -- Pathogenesis -- Periodicals; 616.462005
• DOI: 10.1155/2015/917945
• Languages: English
• ISSNs: 2314-6745

Abstract

Abstract : We hypothesised that tumour necrosis factor- α (TNF- α ) may enhance receptor activator of nuclear factor- κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF- α (anti-TNF- α ). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05 ), there was a significant increase in the area of resorption on the surface (p < 0.01 ) and under the surface (p < 0.01 ) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF- α resulted in a significant reduction in the area of resorption on the surface (p < 0.05 ) and under the surface (p < 0.05 ) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF- α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy.