OSTEOCLAST BIOLOGY - LESSONS FROM MAMMALIAN MUTATIONS
OSTEOCLAST BIOLOGY - LESSONS FROM MAMMALIAN MUTATIONS
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DOI：
10.1002/ajmg.1320340110
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发表时间：
1989-09-01
期刊：
影响因子：
--
通讯作者：
MARKS, SC
中科院分区：
文献类型：
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作者：
MARKS, SC
哺乳动物中的破骨细胞突变的实验研究对破骨细胞生物学做出了重大贡献并得到了证实。先天性骨质疏松症是一种骨骼疾病，其特征是由于破骨细胞功能降低而导致骨骼质量普遍增加。骨骼生长异常、骨髓腔发育和牙齿萌出失败是异质性原因导致的骨吸收减少的继发原因。破骨细胞的致病途径的阐明和细胞生物学的解体是齐头并进的。突变之间破骨细胞的不同分化和激活，以及某些动物和儿童的疾病可以通过骨髓移植为破骨细胞提供合格的干细胞来治愈，这就说明了这一点。儿童先天性缺乏碳酸氢酶II(CA II)会导致一种综合征，包括骨化症，因为在没有CA II的情况下，破骨细胞无法发挥作用。所有突变对甲状旁腺激素的高钙化效应的抵抗力，以及最近报道的血液中1，25二羟基维生素D水平的升高，拓宽了骨石化的发病可能性和破骨细胞的调节可能性。免疫效应，包括自然杀伤细胞活性的降低，超氧化物和白细胞介素2的产生，使骨质疏松突变体成为研究免疫系统在破骨细胞生物学中作用的潜在模型。此外，骨化病与软骨病和成骨细胞异常的共存，以及细胞移植在某些突变中未能治愈疾病，说明了骨玫瑰在探索基质作为破骨细胞生物学导师的作用方面的作用。因此，对先天性骨质疏松症和破骨细胞生物学的了解可能会继续下去。
Major contributions to and confirmations of osteoclast biology have been made by experimental investigations of the osteopetrotic mutations in mammals. Congenital osteopetrosis is a bone disease characterized by a generalized increase in skeletal mass due to decreased osteoclast function. Abnormalities of skeletal growth and the failures of marrow cavity development and tooth eruption are secondary to reduced bone resorption of heterogeneous cause. Elucidation of pathogenetic pathways and unraveling of the cell biology of the osteoclast have proceeded hand‐in‐hand. This is illustrated by the variable differentiation and activation of osteoclasts among mutations and by demonstrations that the disease in certain animals and children can be cured by providing competent stem cells for osteoclasts via bone marrow transplantation. Congenital absence of carbonic anhydrase II (CA II) in children results in a syndrome that included osteopetrosis because osteoclasts are unable to function in the absence of CA II. The resistance of all mutations to the hypercalcemic effects of parathyroid hormone and recent reports of elevated blood levels of 1,25 dihydroxyvitamin D have broadened the scope of pathogenetic possibilities for osteopetrosis and regulatory possibilities for osteoclasts. Immunological effects including reductions in natural killer cell activity, superoxide and interleukin‐2 production make osteopetrotic mutants potential models for studying the role of the immune system in osteoclast biology. Furthermore, coexistence of osteopetrosis with rickets and osteoblast abnormalities and the failure of cell transplants to cure the disease in some mutations illustrate the utility of the osteopetroses for exploring the role of matrix as mentor in osteoclast biology. Thus, understanding congenital osteopetrosis and osteoclast biology are likely to continue together.