MORPHOLOGICAL EVIDENCE OF REDUCED BONE-RESORPTION IN THE OSTEOSCLEROTIC (OC) MOUSE
MORPHOLOGICAL EVIDENCE OF REDUCED BONE-RESORPTION IN THE OSTEOSCLEROTIC (OC) MOUSE
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DOI：
10.1002/aja.1001720204
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发表时间：
1985-01-01
影响因子：
--
通讯作者：
MARKS, SC
中科院分区：
文献类型：
--
作者：
SEIFERT, MF;MARKS, SC
骨石症是一种以骨骼全身硬化为特征的代谢性骨病，在许多哺乳动物物种中以常染色体隐性遗传。先天性石骨病的发病机制是由于破骨细胞功能下降导致骨吸收减少介导的。这一假设是基于迄今为止检查的所有突变中骨吸收减少的功能和结构证据。研究人员对致命性骨硬化突变小鼠——骨硬化（oc）小鼠的软骨和骨的组织学、破骨细胞的超微结构以及矿化骨表面的形态进行了检查。组织学上，oc小鼠的骨骺软骨生长板，特别是肥大区明显增厚，干骺端含有过多的类骨质，这是佝偻病的特征。透射电子显微镜显示，oc 小鼠中 < 1/4 的破骨细胞表现出褶皱边界形成的证据，而正常同窝小鼠中只有 3/4 的破骨细胞出现这种情况。在突变体中，褶皱边界不那么复杂，细胞质过程渗透到骨表面，这表明骨可能是通过机械而不是酶促方式去除的。几乎没有软骨退化的形态学证据，突变体中仍然存在宽阔的限制层。通过扫描电子显微镜观察，正常小鼠经历骨吸收的矿化表面在突变体中没有显示出骨吸收的证据。脊柱病的存在、骨吸收减少的观察以及破坏基质对骨吸收减少的可能贡献是骨硬化突变的特征，这表明它是一种独特的骨硬化突变体，可以在其中研究骨骼代谢的发育和调节。
Osteopetrosis, a metabolic bone disease characterized by a generalized sclerosis of the skeleton, is inherited as an autosomal recessive in a number of mammalian species. The pathogenesis of congenital osteopetrosis is mediated by a reduction in bone resorption as a result of decreased osteoclast function. This hypothesis is based on both functional and structural evidence of reduced bone resorption in all mutations examined to date. The histology of cartilage and bone, the ultrastructure of osteoclasts and the morphology of mineralized bone surfaces in a lethal osteopetrotic mutation, the osteosclerotic (oc) mouse, were examined. Histologically, epiphyseal cartilage growth plates, especially the hypertrophic zone, are markedly thickened in oc mice and metaphyses contain excessive osteoid, features characteristic of rickets. Transmission electron microscopy revealed that < 1/4 of osteoclasts in oc mice demonstrated evidence of ruffled border formation compared with 3/4 of the osteoclasts in normal littermates. In mutants, ruffled borders were less elaborate and cytoplasmic processes penetrated into bone surfaces, suggesting that bone may be removed by mechanical rather than by enzymatic means. There was little morphological evidence of cartilage degradation and broad laminae limitantes persisted in mutants. Mineralized surfaces that undergo resorption in normal mice showed no evidence of bone resorption by scanning electron microscopy in mutants. The presence of a rachitic condition, the observations of reduced bone resorption and the possible contribution of undermineralized matrices to decreased bone resorption are characteristics of the osteosclerotic mutation which suggest that it is a unique osteopetrotic mutant in which to study both the development and regulation of skeletal metabolism.