The possible mechanism of alveolar bone destruction induced by constituent of gram-negative bacteria.

革兰氏阴性菌成分引起牙槽骨破坏的可能机制。

• 批准号: 15592144
• 负责人: SHUHUA Yang
• 金额: $ 2.18万
• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592144/
• 关键词: periodontal disease; muramyldipeptide; lipopolysaccharide; inflammatory cytokine; Toll-like receptor; bone resorption; osteoblast; osteoclast; ムラミルジペプチド; RANKL; OPG; マクロファージ; インターロイキン1

Muramyl dipeptide (MDP) is the minimal essential structural unit responsible for the immunoadjuvant activity of peptidoglycan. As well as bone-resorbing factors such as 1α,25-dihydroxyvitamin D_3 [1α,25(OH)_2D_3] and PGE_2, lipopolysaccharide (LPS) and IL-1α stimulate osteoclast formation in mouse cocultures of primary osteoblasts and hemopoietic cells. MDP alone could not induce osteoclast formation in the coculture, but enhanced osteoclast formation induced by LPS, IL-1α or TNF-α but not 1α,25(OH)_2D_3 or PGE_2. MDP failed to enhance osteoclast formation from osteoclast progenitors induced by receptor activator of NF-κB ligand (RANKL) or TNF-α. MDP up-regulated RANKL expression in osteoblasts treated with LPS or TNF-α but not 1α,25(OH)_2D_3. Osteoblasts expressed mRNA of Nod2, an intracellular sensor of MDP, in response to LPS, IL-1α or TNF-α but not 1α,25(OH)_2D_3. Induction of Nod2 mRNA expression by LPS but not by TNF-α in osteoblasts was dependent on Toll-like receptor (TLR) 4 and myeloid differentiation factor 88 (MyD88). MDP also enhanced TNF-α-induced osteoclast formation in cocultures prepared from Toll-IL-1 receptor domain-containing adapter protein (TIRAP)-deficient mice through the up-regulation of RANKL mRNA expression in osteoblasts, suggesting that TLR2 is not involved in the MDP-induced osteoclast formation. The depletion of intracellular Nod2 by small interfering RNA blocked MDP-induced up-regulation of RANKL mRNA in osteoblasts. LPS and RANKL stimulated the survival of osteoclasts, and this effect was not enhanced by MDP. These results suggest that MDP synergistically enhances osteoclast formation induced by LPS, IL-1α and TNF-α through RANKL expression in osteoblasts, and that Nod2-mediated signals are involved in the MDP-induced RANKL expression hi osteoblasts.

Muramyl二肽（MDP）是负责免疫辅助因子的最小ES科学结构单元，例如1α，25-二羟基乙胺蛋白D_3 [1α，25（OH）_2D_3]在小鼠的原发性成骨细胞和肢体细胞的小鼠共培养中，在共培养中的rm培养在用LPS或TNF-α处理的成骨细胞中，但不是1α，25（OH）_2D_3。区分因子88（MyD88）。小型干扰RNA阻断了MDP诱导的rankl mRNA在成骨细胞中的上升级。参与MDP诱导的RANKL表达HI骨细胞。

项目成果

Experimental spinal fusion with recombinant human bone morphogenetic Protein-2 delivered by a synthetic polymer and beta-tricalcium phosphate in a rabbit model.

在兔模型中使用合成聚合物和 β-磷酸三钙传递的重组人骨形态发生蛋白 2 进行实验性脊柱融合。

• 发表时间: 2005
• 期刊: Spine 30
• 作者: Namikawa T;Terai H;Suzuki E;Nakamura H;Takaoka K.
• 通讯作者: Takaoka K.

Arthritis Research : Methods and Protocols

关节炎研究：方法和方案

• 发表时间: 2005
• 作者: Sato N;et al.;Suda K et al.;Sato N et al.;Takahashi N et al.
• 通讯作者: Takahashi N et al.

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）。

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

MyD88 而不是 TRIP 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。

• 发表时间: 2004
• 期刊: J Exp Med 200
• 作者: Sato N;et al.
• 通讯作者: 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)。