The influence of serum cytokines and growth factors on osteoclast formation in Paget's disease
The influence of serum cytokines and growth factors on osteoclast formation in Paget's disease
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DOI：
10.1093/qjmed/95.4.233
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发表时间：
2002-04-01
影响因子：
13.3
通讯作者：
Athanasou, NA
中科院分区：
文献类型：
--
作者：
Neale, SD;Schulze, E;Athanasou, NA
背景：破骨细胞是多核细胞 (MNC)，由循环单核前体在核因子 kappaB-配体受体激活剂 (RANKL) 和巨噬细胞集落刺激因子 (M-CSF) 存在下形成。目的：确定细胞因子和生长因子是否影响 RANKL/M-CSF 诱导的佩吉特病破骨细胞生成和骨吸收。设计：前瞻性病例对照研究。方法：检测 13 名佩吉特病患者和 8 名正常对照者的 M-CSF、白细胞介素 (IL)-1β、IL-6 和肿瘤坏死因子-α (TNFα) 的血清水平。还评估了佩吉特病患者血清对破骨细胞形成的影响。结果：佩吉特病患者和正常对照者的血清IL-1β、IL-6和TNFα水平较低或检测不到。目前未接受治疗的佩吉特患者的 M-CSF 水平显着升高。在接受佩吉特治疗的患者中，血清 M-CSF 水平与正常对照没有显着差异。在正常单核细胞培养物中，添加未经治疗的佩吉特氏病患者的血清会剂量依赖性地增加 RANKL 诱导的破骨细胞形成和腔隙吸收；上清液中发现 IL-6 水平升高，并且添加人 IL-6 特异性抗体可阻止破骨细胞形成和吸收的增加。未经治疗的佩吉特病患者的血清在缺乏外源性 M-CSF 的情况下也能诱导破骨细胞形成。一种针对人 M-CSF 的特异性抗体消除了这种效应。讨论：M-CSF 和 IL-6 在佩吉特病的破骨细胞形成和骨吸收中发挥着重要作用，血清 M-CSF 的测量可以提供疾病活动性的有用指标。
Background: Osteoclasts are multinucleated cells (MNCs) that form from circulating mononuclear precursors in the presence of the receptor activator of nuclear factor kappaB-ligand (RANKL) and macrophage-colony stimulating factor (M-CSF).Aim: To determine whether cytokines and growth factors influence RANKL/M-CSF induced osteoclastogenesis and bone resorption in Paget's disease.Design: Prospective case-control study.Methods: Serum levels of M-CSF, interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNFalpha) were measured in 13 Paget's disease patients and 8 normal controls. The effect of serum from Paget's patients on osteoclast formation was also assessed.Results: Serum levels of IL-1beta, IL-6 and TNFalpha were low or undetectable in Paget's disease patients and normal controls. Levels of M-CSF were significantly increased in Paget's patients who were not currently under treatment. In Paget's patients under treatment, serum M-CSF levels were not significantly different from normal controls. The addition of serum from untreated Paget's patients dose-dependently increased RANKL-induced osteoclast formation and lacunar resorption in normal monocyte cultures; elevated IL-6 levels were found in the supernatant and the addition of a specific antibody to human IL-6 blocked the increase in osteoclast formation and resorption. Serum from untreated Paget's patients also induced osteoclast formation in the absence of exogenous M-CSF; an antibody specific to human M-CSF abolished this effect.Discussion: Both M-CSF and IL-6 play a major role in osteoclast formation and bone resorption in Paget's disease and measurement of serum M-CSF may provide a useful indicator of disease activity.