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

骨质疏松症是一种遗传性疾病，其特征是由于骨骼分辨率减少而导致骨骼质量增加。据报道，骨质膜OP/OP小鼠的破骨细胞缺乏症是由于M-CSF基因的编码区域的突变引起的。使用OP/OP小鼠，我们探索了破骨细胞在由骨形态发生蛋白（BMP）诱导的生态骨形成中的作用。将含有人重组BMP-2的胶原蛋白海绵盘植入OP/OP和野生型小鼠的背肌袋中3周。每天将双膦酸盐（Risdronate）注入OP/OP和野生型小鼠3周。通过单能X射线绝对测定法测量每个小骨的骨矿物质密度。还进行了定量的组织形态学分析。 OP/OP小鼠中BMP诱导的异位骨的骨矿物质密度比野生型小鼠高约3倍。组织学检查表明，BMP在OP/OP小鼠中诱导了更高的小梁骨形成，而不是在野外……更多的 - 型小鼠。有趣的是，在OP/OP小鼠中形成的Ecopic骨骼的外围表面非常粗糙，而在野生型小鼠中，表面表现出光滑的表面。双膦酸盐治疗进一步增强了OP/OP小鼠的异位骨形成。我们先前报道说，在骨蛋白酶（OPG）缺乏小鼠中，RANKL的血清水平显着升高，但双膦酸盐施用不影响。出乎意料的是，OP/OP小鼠中RANKL的血清水平与OPG缺陷型小鼠中的血清水平高，而野生型小鼠中的RANKL水平水平高，而RANKL分析中的RANKL水平水平则低于可检测到的水平。双膦酸盐治疗对OP/OP小鼠的治疗急剧降低了血清RANKL的升高。这些结果表明，在没有破骨细胞的情况下，BMP诱导的异位骨形成准确地增强了，并且在正常的骨形态发生中包括破骨细胞。我们的结果还表明，双膦酸盐可能直接参与骨骼形成，而无需抑制破骨骨骼骨骼。进一步的研究将阐明BMP诱导的破骨细胞缺乏小鼠中双膦酸盐作用的机制。

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：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

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：
期刊：
影响因子：
0
作者：
通讯作者：

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.

Suda K.et al.: "Suppression of osteoprotegerin expression by prostaglandin E_2 is crucially involved in LPS-induced osteoclast formation."Journal of Immunology. 172・4. 2504-2510 (2004)

Suda K.等人：“前列腺素E_2对骨保护素表达的抑制对于LPS诱导的破骨细胞形成至关重要。”免疫学杂志172·4（2004）。