Itonaga I, Hussein I, Kudo O, Sabokbar A, Watt-Smith S, Ferguson D, Athanasou N A
Nuffield Department of Orthopaedic Surgery, University of Oxford, Windmill Road, Headington, Oxford OX3 7LD, UK.
J Oral Pathol Med. 2003 Apr;32(4):224-31. doi: 10.1034/j.1600-0714.2003.00069.x.
Giant cell granuloma (GCG) is an osteolytic tumour of the jaw which is characterised by the presence of both mononuclear and multinucleated (osteoclast-like) giant cell components. The nature of these component cells and the pathogenesis of the extensive osteolysis associated with this lesion is uncertain.
Using cell culture techniques and immunohistochemistry, we defined the phenotypic characteristics of the mononuclear and multinucleated cells present in four cases of GCG of the jaw. We also analysed the cellular and humoral factors associated with osteoclast formation and osteolysis in these tumours and determined whether GCG stromal cells are capable of supporting osteoclast formation.
GCG-derived giant cells expressed the phenotypic characteristics of osteoclasts (TRAP+, VNR+, and calcitonin responsive) and were capable of lacunar resorption. In addition to macrophages, the mononuclear cell population contained numerous spindle-shaped stromal cells which proliferated in culture and expressed RANKL; these GCG-stromal cells were capable of supporting human osteoclast formation from circulating monocyte precursors.
Our findings indicate that the giant cells in GCG of the jaw are osteoclast-like and formed from monocyte/macrophage precursors which differentiate into osteoclasts under the influence of RANKL-expressing mononuclear stromal cells found in this lesion.
巨细胞肉芽肿(GCG)是颌骨的一种溶骨性肿瘤,其特征是存在单核和多核(破骨细胞样)巨细胞成分。这些组成细胞的性质以及与该病变相关的广泛骨溶解的发病机制尚不清楚。
我们采用细胞培养技术和免疫组织化学方法,确定了4例颌骨GCG中存在的单核和多核细胞的表型特征。我们还分析了与这些肿瘤中破骨细胞形成和骨溶解相关的细胞和体液因子,并确定GCG基质细胞是否能够支持破骨细胞形成。
GCG来源的巨细胞表达破骨细胞的表型特征(抗酒石酸酸性磷酸酶阳性、玻连蛋白受体阳性且对降钙素反应),并能够进行陷窝吸收。除巨噬细胞外,单核细胞群体包含许多梭形基质细胞,这些细胞在培养中增殖并表达核因子κB受体活化因子配体(RANKL);这些GCG基质细胞能够支持循环单核细胞前体形成人破骨细胞。
我们的研究结果表明,颌骨GCG中的巨细胞是破骨细胞样的,由单核细胞/巨噬细胞前体形成,这些前体在该病变中表达RANKL的单核基质细胞的影响下分化为破骨细胞。