Mabilleau G, Petrova N L, Edmonds M E, Sabokbar A
Nuffield Department of Orthopaedic Surgery, Botnar Research Centre, University of Oxford, Oxford, UK.
Diabetologia. 2008 Jun;51(6):1035-40. doi: 10.1007/s00125-008-0992-1. Epub 2008 Apr 4.
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).
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.
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.
目的/假设：我们的目的是比较急性夏科氏关节病患者与糖尿病患者及健康对照者之间的破骨细胞活性，并确定核因子κB受体活化因子配体（RANKL）及其诱饵受体骨保护素（OPG）的作用。
从9名糖尿病夏科氏病患者、8名糖尿病对照者和8名健康对照者中分离出外周血单核细胞，分别在单独存在巨噬细胞集落刺激因子（M-CSF）、M-CSF和RANKL以及M-CSF和RANKL加过量OPG的条件下进行培养。通过玻璃盖玻片上抗酒石酸酸性磷酸酶的表达以及牙本质切片上的吸收情况来评估破骨细胞的形成。
在含有M-CSF的培养物中，与健康对照者和糖尿病对照者相比，夏科氏病患者的破骨细胞形成显著增加（p = 0.008）。与健康对照者和糖尿病对照者相比，前者的骨吸收也显著增加（p < 0.0001）。在含有M-CSF的培养物中添加RANKL后，夏科氏病患者（从0.264±0.06%增至41.6±8.1%，p < 0.0001）、糖尿病对照者（从0.000±0.00%增至14.2±16.5%，p < 0.0001）以及健康对照者（从0.004±0.01%增至10.5±1.9%，p < 0.0001）的破骨细胞吸收均显著增加。虽然在含有M-CSF和RANKL的培养物中添加OPG后，夏科氏病患者的吸收显著减少（从41.6±8.1%降至5.9±2.4%，p = 0.001），但这种抑制不如糖尿病对照者（从14.2±16.5%降至0.45±0.31%，p = 0.001）和健康对照者（从10.5±1.9%降至0.00±0.00%，p <
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