Increased osteoclastic activity in acute Charcot's osteoarthropathy: 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). M...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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Springer-Verlag
2008
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| _version_ | 1797079118809923584 |
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| author | Mabilleau, G Petrova, N Edmonds, M Sabokbar, A |
| author2 | European Association for the Study of Diabetes (EASD) |
| author_facet | European Association for the Study of Diabetes (EASD) Mabilleau, G Petrova, N Edmonds, M Sabokbar, A |
| author_sort | Mabilleau, G |
| collection | OXFORD |
| description | 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%, p0.0001). 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. |
| first_indexed | 2024-03-07T00:41:09Z |
| format | Journal article |
| id | oxford-uuid:8313bfd6-87f3-448e-a360-af79db318f73 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:41:09Z |
| publishDate | 2008 |
| publisher | Springer-Verlag |
| record_format | dspace |
| spelling | oxford-uuid:8313bfd6-87f3-448e-a360-af79db318f732022-03-26T21:41:50ZIncreased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligandJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8313bfd6-87f3-448e-a360-af79db318f73DiabetesOrthopaedicsEnglishOxford University Research Archive - ValetSpringer-Verlag2008Mabilleau, GPetrova, NEdmonds, MSabokbar, AEuropean Association for the Study of Diabetes (EASD)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%, p0.0001). 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. |
| spellingShingle | Diabetes Orthopaedics Mabilleau, G Petrova, N Edmonds, M Sabokbar, A Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand |
| title | Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand |
| title_full | Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand |
| title_fullStr | Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand |
| title_full_unstemmed | Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand |
| title_short | Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand |
| title_sort | increased osteoclastic activity in acute charcot s osteoarthropathy the role of receptor activator of nuclear factor kappab ligand |
| topic | Diabetes Orthopaedics |
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