Hirayama T, Sabokbar A, Itonaga I, Watt-Smith S, Athanasou N A
Department of Pathology, Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.
J Pathol. 2001 Dec;195(5):624-30. doi: 10.1002/path.989.
Gorham-Stout disease (GSD) is a rare, massively osteolytic condition which is associated with increased vascularity and an increase in osteoclast numbers. To determine the cellular and humoral mechanisms underlying the increase in osteoclast numbers and osteolysis in GSD, this study analysed circulating osteoclast precursor numbers and sensitivity to osteoclastogenic factors in a GSD patient and age/sex-matched controls. Monocytes were cultured with M-CSF (25 ng/ml) and RANKL (30 ng/ml) and osteoclast formation was assessed in terms of the formation of TRAP(+) and VNR(+) multinucleated cells and the extent of lacunar resorption. There was no increase in the proportion of circulating osteoclast precursors in GSD relative to controls, but lacunar resorption was consistently greater in GSD monocyte cultures. Increased osteoclast formation in GSD was noted when monocytes were incubated with IL-1beta (1 ng/ml), IL-6/sIL-6R (100 ng/ml), and TNFalpha (10 ng/ml). An increase in osteoclast differentiation and bone resorption was also noted in control monocyte cultures in the presence of GSD serum. These results indicate that the increase in osteoclast formation in GSD is due not to an increase in the number of circulating osteoclast precursors, but rather to an increase in the sensitivity of these precursors to humoral factors which promote osteoclast formation and bone resorption.
戈勒姆-斯托特病（GSD）是一种罕见的、具有大量骨质溶解的病症，与血管增多和破骨细胞数量增加有关。为了确定GSD中破骨细胞数量增加和骨质溶解背后的细胞和体液机制，本研究分析了一名GSD患者以及年龄/性别匹配的对照者循环破骨细胞前体数量和对破骨细胞生成因子的敏感性。将单核细胞与M-CSF（25 ng/ml）和RANKL（30 ng/ml）一起培养，并根据TRAP(+)和VNR(+)多核细胞的形成以及腔隙吸收程度评估破骨细胞形成。与对照组相比，GSD患者循环破骨细胞前体的比例没有增加，但GSD单核细胞培养物中的腔隙吸收始终更大。当单核细胞与IL-1β（1 ng/ml）、IL-6/sIL-6R（100 ng/ml）和TNFα（10 ng/ml）一起孵育时，发现GSD中破骨细胞形成增加。在存在GSD血清的情况下，对照单核细胞培养物中也观察到破骨细胞分化和骨吸收增加。这些结果表明，GSD中破骨细胞形成的增加不是由于循环破骨细胞前体数量的增加，而是由于这些前体对促进破骨细胞形成和骨吸收的体液因子的敏感性增加。
