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Journal of Diabetes Research
Volume 2015 (2015), Article ID 917945, 10 pages
http://dx.doi.org/10.1155/2015/917945
Research Article

Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy

1Diabetic Foot Clinic, King’s College Hospital, London SE5 9RS, UK
2Department of Materials, Imperial College London, London SW7 2AZ, UK
3Cardiovascular Division, King’s College London, London SE5 9NU, UK

Received 12 February 2015; Revised 23 April 2015; Accepted 23 April 2015

Academic Editor: Andrea Scaramuzza

Copyright © 2015 Nina L. Petrova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 (), there was a significant increase in the area of resorption on the surface () and under the surface () 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 () and under the surface () 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.