Inhibition of tnf-α reverses the pathological resorption pit profile of osteoclasts from patients with acute charcot osteoarthropathy

TY - JOUR

T1 - Inhibition of tnf-α reverses the pathological resorption pit profile of osteoclasts from patients with acute charcot osteoarthropathy

AU - Petrova, Nina L.

AU - Petrov, Peter K.

AU - Edmonds, Michael E.

AU - Shanahan, Catherine M.

PY - 2015

Y1 - 2015

N2 - We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-β 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.

AB - We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-β 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.

UR - http://www.scopus.com/inward/record.url?scp=84934939442&partnerID=8YFLogxK

U2 - 10.1155/2015/917945

DO - 10.1155/2015/917945

M3 - Article

C2 - 26137498

AN - SCOPUS:84934939442

SN - 2314-6745

VL - 2015

JO - Journal of Diabetes Research

JF - Journal of Diabetes Research

M1 - 917945

ER -