Analysis of molecular mechanisms in bone formation and regeneration

骨形成和再生的分子机制分析

• 批准号: 14207075
• 负责人: OZAWA Hidehiro
• 金额: $ 32.12万
• 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 (A)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14207075/
• 关键词: Calcification; Bone formation; Bone resorption; Coupling factor; MyD88; Dental pulp; Laser; EP4 agonist; BMP; OPG; EP4; 急速凍結法

I. Molecular mechanisms of calcification in bone matrix formation : To identify the factor induce formation of the nuclear, we make monoclonal anti-body using matrix vesicle isolated from MLO-A5 cell in culture and clarified that the antigen localizes among the fibrae in extracellular matrix. Moreover, to estimate the effects of Mg in bone calcification, we determined the bone qualities, especially mineralization in Mg deficient rat. Loss of Mg was increased the value of Ca and had irregular crystal of hydroxyapatite in the rat. These findings indicate that the loss of Mg inhibits the crystallization of hydroxyapatite in matrix vesicle.II. Coupling mechanisms of bone metabolism : Bone formation and bone resorption were promoted in osteoprotegerin (OPG)-deficient mice. Bisphosphonate, a potential inhibitor of bone resorption, reduced both bone formation and bone resorption. Bone formation induced by bone morphogenetic protein in OPG-deficient mice did not exhibit any difference from tha … More t in wild mice. These results suggest that coupling factors activated or released by osteoclasts may be involved in the subsequent bone formation. We investigated the mechanism of osteoclastogenesis induced by lipopolysaccharide and interleukin (IL)-1. These factors induced the expression of RANKL in osteoblastic cells through MyD 88 and Ca/PKC-MEK/ERK pathways.III. Bone regeneration and reconstruction model : The subcutaneously transplanted rat dental pulp formed mineralized hard tissue possessing bone- or cementum-like characteristics, suggesting that dental pulp possesses the ability to hard tissue formation by itself. Bone formation induced laser light irradiation was shown to be caused by the odontoblast activation and the inhibition of osteoclastic bone resorption. In the study of prostaglandin E EP4 receptor agonist, the gene expression existed in odontoblast, and the bone formation activity was resulted from the decrease of adipocyte and the increase of osteoblast in bone marrow. Less

I.骨基质形成中钙化的分子机制：为了鉴定诱导核形成的因子，我们用从培养的MLO-A5细胞中分离的基质囊泡制备了单克隆抗体，并阐明了抗原定位于细胞外基质中的纤维之间。此外，为了评价镁在骨钙化中的作用，我们测定了缺镁大鼠的骨质量，特别是矿化。镁的丢失使钙含量增加，羟基磷灰石结晶不规则。这些结果表明，镁的损失抑制了基质囊泡中羟基磷灰石的结晶。骨代谢偶联机制：骨保护素（OPG）缺陷小鼠骨形成和骨吸收促进。双膦酸盐是一种潜在的骨吸收抑制剂，可减少骨形成和骨吸收。骨形态发生蛋白诱导的骨形成在OPG缺陷小鼠中与对照组无任何差异。 ...更多信息 t在野生小鼠中。这些结果提示破骨细胞激活或释放的偶联因子可能参与了随后的骨形成。我们研究了脂多糖和白细胞介素（IL）-1诱导破骨细胞生成的机制。这些因子通过MyD 88和Ca/PKC-MEK/ERK途径诱导成骨细胞表达RANKL。骨再生与重建模型：大鼠牙髓皮下移植后形成具有骨样或牙骨质样特征的矿化硬组织，提示牙髓具有自身硬组织形成的能力。激光照射诱导成骨作用是通过激活成牙本质细胞和抑制成骨细胞的骨吸收而实现的。在前列腺素E EP 4受体激动剂的研究中，成牙本质细胞中存在基因表达，骨髓中脂肪细胞减少，成骨细胞增加是导致成骨活性的原因。少

项目成果

Effect of estrogen deficiency on osteoclastogenesis in rat peiodontium.

雌激素缺乏对大鼠牙骨质破骨细胞生成的影响。

• 发表时间: 2002
• 期刊: Arch Oral Biol 47
• 作者: Kawamoto S.;et al.
• 通讯作者: et al.

Bone morphogenetic protein 2-induced osteoblast differentiation requires smad-mediated down-regulation of Cdk6

• DOI: 10.1128/mcb.24.15.6560-6568.2004
• 发表时间: 2004-08-01
• 期刊: MOLECULAR AND CELLULAR BIOLOGY
• 影响因子: 5.3
• 作者: Ogasawara, T;Kawaguchi, H;Okayama, H
• 通讯作者: Okayama, H

Takahashi N et al.: "Principles of Bone Biology, Second Edition, Volume 1"Academic press. 882 (2002)

高桥N等：《骨生物学原理，第二版，第1卷》学术出版社。

Expression of Notch in a case of osteosarcoma of the maxilla.

Notch在一例上颌骨骨肉瘤中的表达。

• 发表时间: 2004
• 期刊: Eur J Med Res. 9(11)
• 作者: Nagatsuka H;Nobuhisa T;Gunduz E;Inoue M;Kawakami T
• 通讯作者: Kawakami T

MyD88 but not TRIF is essential for osteoclastogenesis induced by lipopolysaccharide, diacyl lipopeptide, and IL-1alpha.

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

• DOI: 10.1084/jem.20040689
• 发表时间: 2004-09-06
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Sato, N;Takahashi, N;Suda, K;Nakamura, M;Yimaki, 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