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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

石骨症是一种遗传性疾病，其特征是由于骨吸收减少而导致骨量增加。据报道，破骨细胞缺乏症在骨硬化op/op小鼠是由于M-CSF基因的编码区的突变。以OP/OP小鼠为研究对象，探讨破骨细胞在骨形态发生蛋白（BMP）诱导异位成骨中的作用。将含有人重组BMP-2的胶原海绵盘植入op/op和野生型小鼠的背肌袋中3周。每天向op/op和野生型小鼠注射双膦酸盐（利塞膦酸盐），持续3周。采用单能X线骨密度仪测量各听小骨的骨密度。还进行了定量组织形态学分析。BMP诱导的异位骨的骨密度在op/op小鼠中比野生型小鼠高约3倍。组织学检查显示BMP诱导OP/OP小鼠比野生型小鼠更高的钙化骨小梁形成 ...更多信息 - 型小鼠。有趣的是，在op/op小鼠中形成的异位骨的周边显示出非常粗糙的表面，而在野生型小鼠中显示出光滑的表面。双膦酸盐治疗进一步增强了op/op小鼠的异位骨形成。我们以前报道过，骨保护素（OPG）缺陷小鼠的血清RANKL水平显著升高，但不受双膦酸盐给药的影响。出乎意料的是，OP/OP小鼠的RANKL血清水平与OPG缺陷小鼠一样高，而野生型小鼠的RANKL血清水平低于RANKL测定的可检测水平。用双膦酸盐治疗op/op小鼠可显著降低升高的血清RANKL水平。这些结果表明，BMP诱导的异位骨形成准确地增强在没有破骨细胞，破骨细胞参与正常的骨形态发生。我们的研究结果还表明，双膦酸盐可能直接参与骨形成，而不抑制骨吸收。进一步的研究将阐明双膦酸盐在破骨细胞缺陷小鼠BMP诱导的骨形成中的作用机制。

项目成果

期刊论文数量（37）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Itoh K.et al.: "LPS promotes the survival of osteoclasts via toll-like receptor 4, but cytokine production of osteoclasts in response to LPS is different from that of macrophages."Journal of Immunology. 170・7. 3688-3695 (2003)

Itoh K.等人：“LPS通过Toll样受体4促进破骨细胞的存活，但破骨细胞响应LPS的细胞因子产生与巨噬细胞不同。”免疫学杂志170・7。 2003）

DOI：
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0
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Muramyl dipeptide enhances osteoclast formation induced by lipopolysaccharide, IL-1α and TNFα through Nod2-mediated signaling in osteoblasts.

Muramyl 二肽通过 Nod2 介导的成骨细胞信号传导增强脂多糖、IL-1α 和 TNFα 诱导的破骨细胞形成。

DOI：
发表时间：
2005
期刊：
J Immunol (in press)
影响因子：
0
作者：
Mizoguchi T et al.;Kobayashi Y et al.;Kobayashi Y et al.;Yang S et al.
通讯作者：
Yang S et al.

Li X.et al.: "p38 MAPK is crucially involved in osteoclast differentiation but not in cytokine production, phagocytosis or dendritic cell differentiation of bone marrow macrophages."Endocrinology. 144・11. 4999-5005 (2003)

Li X. 等人：“p38 MAPK 与破骨细胞分化密切相关，但与骨髓巨噬细胞的细胞因子产生、吞噬作用或树突状细胞分化无关。” 144・11 (2003)。

DOI：
发表时间：
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0
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MyD88 but not TRIF is essential for osteoclastogenes is induced by lipopolysaccharide, diacyl lipopeptide, and IL-1α.

MyD88 而不是 TRIF 对于脂多糖、二酰基脂肽和 IL-1α 诱导的破骨细胞至关重要。

DOI：
发表时间：
2004
期刊：
Journal of Experimental Medicine 200(5)
影响因子：
0
作者：
Sato N;Takahashi N;Suda K;Nakamura M;Yamaki M;Ninomiya T;Kobayashi Y;Takada H;Shibata K;Yamamoto M;Takeda K;Akira S;Noguchi T;Udagawa N.
通讯作者：
Udagawa N.

骨吸収と骨形成の共役機構

骨吸收与骨形成的耦合机制