Marks S C, Popoff S N
Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655.
Am J Anat. 1989 Dec;186(4):325-34. doi: 10.1002/aja.1001860402.
Osteopetrosis is a metabolic bone disease characterized by reduced bone resorption. From experimental studies of various osteopetrotic mutations has emerged the hypothesis that each is unique with respect to mechanisms whereby osteoclast development and/or function are reduced. The osteopetrotic (op) mutation in the rat was discovered in Fatty/ORL stock over a decade ago. The paucity of data about osteoclast biology in this mutation prompted this study of cytological, cytochemical, and ultrastructural features of osteoclasts. In op rats, osteoclasts are significantly reduced in number, but are larger and more vacuolated than in normal littermates. Mutant osteoclasts can form ruffled borders and clear zones, but their ability to fragment and excavate bone surfaces is greatly impaired. Cytoplasmic vacuoles in op osteoclasts are randomly distributed and greatly enlarged, and they stain weakly for two cytochemical characteristics of osteoclasts, tartrate-resistant acid phosphatase and acid ATPase. These findings suggest that an abnormality in the lysosomal/vacuolar system, an important component of the resorptive mechanism, may be involved in the interception of osteoclast function in this mutation.
骨质石化症是一种以骨吸收减少为特征的代谢性骨病。通过对各种骨质石化症突变的实验研究，出现了一种假说，即每种突变在破骨细胞发育和/或功能降低的机制方面都是独特的。大鼠的骨质石化症（op）突变是十多年前在Fatty/ORL品系中发现的。关于这种突变中破骨细胞生物学的数据匮乏促使了对破骨细胞的细胞学、细胞化学和超微结构特征的研究。在op大鼠中，破骨细胞数量显著减少，但比正常同窝仔鼠的破骨细胞更大且空泡化程度更高。突变的破骨细胞可以形成皱襞缘和清亮区，但其破碎和挖掘骨表面的能力受到极大损害。op破骨细胞中的细胞质空泡随机分布且大大增大，并且它们对破骨细胞的两种细胞化学特征——抗酒石酸酸性磷酸酶和酸性ATP酶——的染色较弱。这些发现表明，溶酶体/液泡系统（吸收机制的一个重要组成部分）的异常可能参与了这种突变中破骨细胞功能的阻断。
