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首页> 外文期刊>American Journal of Physiology >High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment
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High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment

机译：慢性糖皮质激素治疗儿童21-羟化酶缺乏症儿童的血清和白细胞中dickkopf-1水平高

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Children with 21-hydroxylase deficiency (21-OHD) need chronic glucocorticoid (cGC) therapy to replace congenital deficit of cortisol synthesis, and this therapy is the most frequent and severe form of drug-induced osteoporosis. In this study, we enrolled 18 patients (9 females) and 18 sex- and age-matched controls. We found in 21-OHD patients high serum and leukocyte levels of dickkopf-1 (DKK1), a secreted antagonist of the Wnt/β-catenin signaling pathway known to be a key regulator of bone mass. In particular, we demonstrated by flow cytometry, confocal microscopy, and real-time PCR that monocytes, T lymphocytes, and neutrophils from patients expressed high levels of DKK1, which may be related to the cGC therapy. In fact, we showed that dexamethasone treatment markedly induced the expression of DKK1 in a dose- and time-dependent manner in leukocytes. The serum from patients containing elevated levels of DKK1 can directly inhibit in vitro osteoblast differentiation and receptor activator of NF-κB ligand (RANKL) expression. We also found a correlation between both DKK1 and RANKL or COOH-terminal telopeptides of type I collagen (CTX) serum levels in 21-OHD patients on cGC treatment. Our data indicated that DKK1, produced by leukocytes, may contribute to the alteration of bone remodeling in 21-OHD patients on cGC treatment.
机译：患有21-羟化酶缺乏症（21-OHD）的儿童需要慢性糖皮质激素（cGC）治疗来替代先天性皮质醇合成的缺乏，并且这种治疗是药物诱发的骨质疏松症的最常见和最严重的形式。在这项研究中，我们招募了18位患者（9位女性）和18位性别和年龄匹配的对照。我们在21位OHD患者中发现dickkopf-1（DKK1）是Wnt /β-catenin信号传导途径的分泌拮抗剂，是血清骨量的关键调节剂，其血清和白细胞水平较高。特别是，我们通过流式细胞术，共聚焦显微镜和实时PCR证实了来自患者的单核细胞，T淋巴细胞和中性粒细胞表达了高水平的DKK1，这可能与cGC治疗有关。实际上，我们显示地塞米松治疗以剂量和时间依赖性方式显着诱导DKK1在白细胞中的表达。来自DKK1水平升高的患者的血清可以直接抑制体外成骨细胞分化和NF-κB配体（RANKL）表达的受体激活剂。我们还在cGC治疗的21-OHD患者中发现了DKK1和RANKL或I型胶原（CTX）的COOH末端端肽水平之间的相关性。我们的数据表明，白细胞产生的DKK1可能有助于21-OHD患者经cGC治疗后骨重塑的改变。

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