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Increased osteoclastic activity in acute Charcot’s osteoarthopathy: the role of receptor activator of nuclear factor-kappaB ligand

AIMS/HYPOTHESIS: Our aims were to compare osteoclastic activity between patients with acute Charcot’s osteoarthropathy and diabetic and healthy controls, and to determine the effect of the receptor activator of nuclear factor-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG). METHOD...

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Detalles Bibliográficos
Autores principales: Mabilleau, G., Petrova, N. L., Edmonds, M. E., Sabokbar, A.
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362134/
https://www.ncbi.nlm.nih.gov/pubmed/18389210
http://dx.doi.org/10.1007/s00125-008-0992-1
Descripción
Sumario:AIMS/HYPOTHESIS: Our aims were to compare osteoclastic activity between patients with acute Charcot’s osteoarthropathy and diabetic and healthy controls, and to determine the effect of the receptor activator of nuclear factor-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG). METHODS: Peripheral blood monocytes isolated from nine diabetic Charcot patients, eight diabetic control and eight healthy control participants were cultured in the presence of macrophage-colony stimulating factor (M-CSF) alone, M-CSF and RANKL, and also M-CSF and RANKL with excess concentrations of OPG. Osteoclast formation was assessed by expression of tartrate-resistant acid phosphatase on glass coverslips and resorption on dentine slices. RESULTS: In cultures with M-CSF, there was a significant increase in osteoclast formation in Charcot patients compared with healthy and diabetic control participants (p = 0.008). A significant increase in bone resorption was also seen in the former, compared with healthy and diabetic control participants (p < 0.0001). The addition of RANKL to the cultures with M-CSF led to marked increase in osteoclastic resorption in Charcot (from 0.264 ± 0.06% to 41.6 ± 8.1%, p < 0.0001) and diabetic control (0.000 ± 0.00% to 14.2 ± 16.5%, p < 0.0001) patients, and also in healthy control participants (0.004 ± 0.01% to 10.5 ± 1.9%, p < 0.0001). Although the addition of OPG to cultures with M-CSF and RANKL led to a marked reduction of resorption in Charcot patients (41.6 ± 8.1% to 5.9 ± 2.4%, p = 0.001), this suppression was not as complete as in diabetic control patients (14.2 ± 16.5% to 0.45 ± 0.31%, p = 0.001) and in healthy control participants (from 10.5 ± 1.9% to 0.00 ± 0.00%, p < 0.0001). CONCLUSIONS/INTERPRETATION: These results indicate that RANKL-mediated osteoclastic resorption occurs in acute Charcot’s osteoarthropathy. However, the incomplete inhibition of RANKL after addition of OPG also suggests the existence of a RANKL-independent pathway.