Gallwitz W E, Mundy G R, Lee C H, Qiao M, Roodman G D, Raftery M, Gaskell S J, Bonewald L F
University of Texas Health Science Center, San Antonio 78284-7877.
J Biol Chem. 1993 May 15;268(14):10087-94.
Bone resorption requires cooperation between osteoclasts and mononuclear accessory cells by mechanisms which have not been elucidated. Since multinucleated cells in giant cell tumors of bone have many phenotypic and functional characteristics of normal osteoclasts, we have examined the interaction between the bone-resorbing multinucleated cells and the distinct mononuclear stromal cells from these tumors. We have found that these mononuclear cells produce an activity which stimulates both giant cells from giant cell tumors and rodent osteoclasts to resorb bone in vitro. We have identified the activity and found that it represents several products of the 5-lipoxygenase pathway of arachidonic acid metabolism, namely 5-hydroxyeicosatetraenoic acid and the leukotrienes. These data indicate that 5-lipoxygenase metabolites stimulate isolated osteoclasts to resorb bone in vitro and may represent a mechanism by which mononuclear stromal cells in human giant cell tumors communicate with the giant cells. In addition, these results may explain a possible mechanism for communication between accessory cells and osteoclasts involved in normal bone resorption.
骨吸收需要破骨细胞与单核辅助细胞通过尚未阐明的机制进行协作。由于骨巨细胞瘤中的多核细胞具有许多正常破骨细胞的表型和功能特征，我们研究了这些肿瘤中骨吸收多核细胞与不同单核基质细胞之间的相互作用。我们发现这些单核细胞产生一种活性物质，该物质在体外既能刺激骨巨细胞瘤的巨细胞，也能刺激啮齿动物破骨细胞进行骨吸收。我们已经鉴定出该活性物质，发现它代表花生四烯酸代谢的5-脂氧合酶途径的几种产物，即5-羟基二十碳四烯酸和白三烯。这些数据表明，5-脂氧合酶代谢产物在体外刺激分离的破骨细胞进行骨吸收，并且可能代表人类骨巨细胞瘤中单核基质细胞与巨细胞之间的一种通讯机制。此外，这些结果可能解释了参与正常骨吸收的辅助细胞与破骨细胞之间通讯的一种可能机制。
