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

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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