Analysis of tooth development of osteoprotegerin- deficient mice

骨保护素缺陷小鼠牙齿发育分析

基本信息

批准号：
15592180
负责人：
NAKAMURA Hiroshi
金额：
$ 2.24万
依托单位：
Matsumoto Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Osteopetrosis is an inherited disorder characterized by an increase in bone mass due to reduced bone resorption. It has been reported that the osteoclast deficiency in osteopetrotic op/op mice is due to a mutation in the coding region of the M-CSF gene. Using op/op mice, we explored roles of osteoclasts in ectopic bone formation induced by bone morphogenetic protein (BMP). Collagen sponge disks containing human recombinant BMP-2 were implanted into the dorsal muscle pouches in op/op and wild-type mice for 3 weeks. Bisphosphonate (risedronate) was injected into op/op and wild-type mice every day for 3 weeks. Bone mineral density of each ossicle was measured by single energy x-ray absorptiometry. Quantitative histomorphometric analysis was also performed. Bone mineral density of BMP-induced ectopic bone in op/op mice was about 3-fold higher than that in wild-type mice. Histological examination revealed that BMP induced higher calcified trabecular bone formation in op/op mice than in wild … More -type mice. Interestingly, the periphery of ectopic bones formed in op/op mice showed extremely rough surface, whereas that in wild-type mice showed smooth ones. Bisphosphonate treatment further enhanced ectopic bone formation in op/op mice. We previously reported that serum levels of RANKL were markedly elevated in osteoprotegerin (OPG)-deficient mice, but were unaffected by bisphosphonate administration. Unexpectedly, serum levels of RANKL in op/op mice were as high as those in OPG-deficient mice, whereas those in wild-type mice were under detectable levels in the RANKL assay. Treatment of op/op mice with bisphosphonate treatment sharply decreased the elevated levels of serum RANKL. These results suggest that BMP-induced ectopic bone formation is accurately enhanced in the absence of osteoclasts, and osteoclasts are involved in normal bone morphogenesis. Our results also suggest that bisphosphonates may be directly involved in bone formation without inhibition of osteoclastic bone resorption. Further studies will elucidate the mechanism of bisphosphonate action in BMP-induced bone formation in osteoclast-deficient mice Less

骨术是一种遗传性疾病，其特征是由于红骨疗法的缺乏，骨质骨骼的缺陷是由于M-CSF基因的编码区域中的突变。异位骨形态发生蛋白（BMP）中的破骨细胞。将BMP-2组合成op/op/op和野生型小鼠的背肌袋中3周骨质的骨质通过单一的X射线吸收量，骨骼的骨骼矿物质密度。与野生的小鼠相比，在OP/OP小鼠中形成的异位骨骼的外围表面非常粗糙，双膦酸盐的布置促进了OP/OP小鼠的异位。在骨蛋白酶（OPG）缺陷小鼠中显着升高，但双膦酸盐不受影响，rankl pmice的水平与OPG-DEF糖尿病小鼠一样RANKL的关联表明，在没有破骨细胞的情况下，BMP诱导的异位骨形成也表明，双膦酸盐可能直接参与骨形成蛋白质的骨肿块，阐明了BMP诱导的骨骼骨骼形成骨磷酸的机械。小鼠少少少