Clarification of Mechanism of the Tendon/Ligament Matrix Remodeling Induced by Various Mesenchymal Cells and Its Molecular Control

阐明多种间充质细胞诱导肌腱/韧带基质重塑的机制及其分子调控

• 批准号: 16390425
• 负责人: YASUDA Kazunori
• 金额: $ 8.83万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390425/
• 关键词: Soft tissues; Tendon; Ligament; Matrix; Remodeling; Fibroblast; Stress deprivation; Molecular control; 徐負荷; 靱帯

1)Stress deprivation significantly enhanced gene expression of Mn-SOD, Tyrosinase-related protein, KIAA1199-related protein, KIAA1199, and PDGFR-alpha in fibroblasts in the patellar tendon. In addition, Mn-SOD was over-expressed in vivo at both the m-RNA and protein levels. Stress deprivation also significantly enhanced expression of Expression of IL-1beta, TNF-alpha, and TGF-beta in the patellar tendon, while it provided no significant effects to expression of PDGF-B and bFGF. In fibroblasts of the grafted tendon, VEGF was over-expressed at 2 weeks and showed a peak at 3 weeks.2)The proliferation rate of extrinsic fibroblasts (EFs) derived from the tendon tissue was significantly lower was significantly lower than that of intrinsic fibroblasts (IFs) in the tendon. The infiltrative rate was significantly higher in EFs than in IFs on 10 to 14 days after cell culture. Ex vivo infiltration of both fibroblasts into the patellar tendon significantly reduced the mechanical properties of fasc … More icles from the tendon.3)An application of TGF-beta1 significantly reduced the deterioration of mechanical properties of the patellar tendon caused by stress deprivation, while an application of anti-TGF-beta antibody significantly enhanced the degradation. Concerning the in situ frozen-thawed anterior cruciate ligament and the grafted patellar tendon, the TGF-beta1 application did not show' any significant effects. Regarding a fibrous tissue regenerated in a defect created in the patellar tendon, the TGF-beta1 application significantly increased the mechanical properties. An application of VEGF to the in situ frozen-thawed ACL significantly enhanced vascular regeneration, while it did not significantly affect the mechanical properties.4)An application of synovial tissue-derived cells cultured in TGF-beta1-suplimented medium significantly increased the mechanical properties of the grafted tendon in ACL reconstruction and the fibrous tissue regenerated in a defect created in the patellar tendon. Less

1)应激剥夺显着增强髌腱成纤维细胞中Mn-SOD、酪氨酸酶相关蛋白、KIAA1199相关蛋白、KIAA1199和PDGFR-α的基因表达。此外，Mn-SOD 在体内 mRNA 和蛋白质水平上均过表达。应力剥夺还显着增强了髌腱中 IL-1β、TNF-α 和 TGF-β 的表达，但对 PDGF-B 和 bFGF 的表达没有显着影响。在移植肌腱的成纤维细胞中，VEGF在2周时过度表达，并在3周时达到峰值。2）来自肌腱组织的外源性成纤维细胞（EF）的增殖率明显低于肌腱内的内在成纤维细胞（IF）。细胞培养后10至14天，EF中的浸润率显着高于IF中。两种成纤维细胞离体浸润到髌腱中，显着降低了肌腱筋膜的机械性能。3）TGF-β1的应用显着减少了应力剥夺引起的髌腱机械性能的恶化，而抗TGF-β抗体的应用显着增强了降解。对于原位冻融的前交叉韧带和移植的髌腱，TGF-β1的应用没有显示出任何显着的效果。对于在髌腱缺陷中再生的纤维组织，TGF-β1 的应用显着提高了机械性能。将VEGF应用于原位冻融的ACL可显着增强血管再生，同时不会显着影响其机械性能。4）应用在添加TGF-β1的培养基中培养的滑膜组织来源的细胞可显着提高ACL重建中移植肌腱的机械性能以及髌骨缺损处再生的纤维组织 肌腱。较少的

项目成果

Radiofrequency energy dramatically reduces the material properties of collagen fascicles in the anterior cruciate ligament.

射频能量极大地降低了前十字韧带中胶原纤维束的材料特性。

• 发表时间: 2005
• 期刊: Trans Orthop Res Soc 30
• 作者: Seki;T.;Namba;T.;Mochizuki;H.;Onodera;M;Yasuda K;D. Yoshida;D. Yoshida;Kondo E
• 通讯作者: Kondo E

Effects of administration of transforming growth factor (TGF) beta-1 and anti-TGF-betal antibody on mechanical properties of the stress-shielded patellar tendon.

施用转化生长因子 (TGF) beta-1 和抗 TGF-beta 抗体对应力屏蔽髌腱机械性能的影响。

• 发表时间: 2006
• 期刊: J Biomechanics 39(14)
• 作者: Hirano F;et al.;Miyatake S;Onodera J;Hirano F;Kobayashi A;Okamoto S;Hirano F;Kondo E;Ju Y-J.;Katsura T.
• 通讯作者: Katsura T.

Local administration of synovium-derived fibroblasts cultured in TGF-betal-supplemented medium inhibits reduction of structural properties of the tendon autograft after anterior cruciate ligament reconstruction : A sheep model study.

局部施用在添加 TGF-β 的培养基中培养的滑膜来源的成纤维细胞可抑制前十字韧带重建后自体肌腱结构特性的降低：一项绵羊模型研究。

• 发表时间: 2007
• 期刊: Trans Orthop Res Soc 32
• 作者: Tsuda;M.;et al.;Ikema Y;Kondo E;Hayashi R;Miyatake S;Okamoto S;Ikema Y.;Kondo E.
• 通讯作者: Kondo E.

Temporal changes in relationship between fibroblast repopulation, VEGF expression and angiogenesis in the patellar tendon graft after anterior cruciate ligament reconstruction

前交叉韧带重建后髌腱移植物中成纤维细胞再生、VEGF表达和血管生成之间关系的时间变化

• 发表时间: 2004
• 期刊: Trans Orthop Res Soc 29
• 作者: Ikeda;T;Ikeda T;Kondo E;Tohyama H;Ikema Y;Kondo E;Katsura T;Uchida H;Tohyama H.;Kondo E.;Yoshikawa T.;Katsura T.;Uchida H;Anaguchi Y;Yamazaki S;Ikema Y;Tohyama H;Kondo E;Kudo T;Yasuda K;Ikema Y;Yoshikawa T
• 通讯作者: Yoshikawa T

Local administration of synovium-derived fibroblasts accelerates extrinsic fibroblast infiltration into the tendon graft after ACL reconstruction, but it results in reduction of structural properties of the graft : A sheep model study.

局部施用滑膜来源的成纤维细胞可加速 ACL 重建后外源性成纤维细胞浸润到肌腱移植物中，但会导致移植物的结构特性降低：一项绵羊模型研究。

• 发表时间: 2006
• 期刊: Trans Orthop Res Soc 31
• 作者: Hirano F;et al.;Miyatake S;Onodera J;Hirano F;Kobayashi A;Okamoto S;Hirano F;Kondo E
• 通讯作者: Kondo E