title: Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy.
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.
authors.affiliation: Diabetic Foot Clinic, King's College Hospital, London SE5 9RS, UK.
authors.forename: Nina L
authors.identifier: 0000-0001-6937-6565
authors.initials: NL
authors.lastname: Petrova
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, UK.
authors.forename: Peter K
authors.identifier: 0000-0003-3643-6685
authors.initials: PK
authors.lastname: Petrov
authors.affiliation: Diabetic Foot Clinic, King's College Hospital, London SE5 9RS, UK.
authors.forename: Michael E
authors.identifier: 0000-0002-8931-0069
authors.initials: ME
authors.lastname: Edmonds
authors.affiliation: Cardiovascular Division, King's College London, London SE5 9NU, UK.
authors.forename: Catherine M
authors.identifier: 0000-0002-8352-8171
authors.initials: CM
authors.lastname: Shanahan
mesh_terms: D000328:Adult; D000368:Aged; D001177:Arthropathy, Neurogenic / Q000209:etiology / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor