Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy
Surface profilometry in Charcot patients, diabetic patients, and healthy control subjects in M-CSF + RANKL-treated cultures and in M-CSF + RANKL + anti-TNF-α-treated cultures. Representative erosion profiles of resorbed bone discs in Charcot patient (blue line), diabetic patient (red line), and healthy control subject (green line) after surface profilometry in M-CSF + RANKL-treated cultures (a) and in M-CSF + RANKL + anti-TNF-α-treated cultures (b). Representative erosion profiles of resorbed bone discs in M-CSF + RANKL-treated cultures (blue line) and M-CSF + RANKL + anti-TNF-α-treated cultures (red line) in Charcot patient (c), diabetic patient (d), and healthy control subject (e). The marked difference of the erosion profile in a Charcot patient compared with diabetic patient and healthy control in MCSF + RANKL-treated cultures (a) was reversed after the addition of anti-TNF-α (b). Pits appeared significantly smaller in M-CSF + RANKL + anti-TNF-α-treated cultures compared with MCSF + RANKL-treated cultures in Charcot patients (c) but remained unchanged in diabetic patients (d) and in healthy controls (e). Comparison of pit measurements (width, FWHM, and depth) between M-CSF + RANKL-treated cultures (white bars) and M-CSF + RANKL + anti-TNF-α-treated cultures (grey bars); unidented pits (f), bidented pits (g), and multidented pits (h). Significance assessed by Mann-Whitney test, levels of significance are demonstrated on the graphs; ; ; ns = nonsignificant (). Distribution of pits (%) according to their shape in M-CSF + RANKL and M-CSF + RANKL + anti-TNF-α-treated cultures in Charcot patients, diabetic patients, and healthy control subjects (i). In M-CSF + RANKL-treated cultures, there was a significant reduction in the percentage of unidented () and a significant increase in the percentage of multidented pits () in Charcot patients compared with diabetic patients and healthy controls. The addition of anti-TNF-α treatment led to a significant difference in the pit distribution only in Charcot patients characterised by a significant increase in the percentage of unidented pits () and significant decrease in the percentage of multidented pits (). No differences in the pit distribution were noted in diabetic patients and in healthy control subjects.
(a) M-CSF + RANKL
(b) M-CSF + RANKL + anti-TNF-α
(f) Unidented pits
(g) Bidented pits
(h) Multidented pits
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