Campbell B H, Agarwal C, Wang J H-C
Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, E1641 Biomedical Science Tower, 210 Lothrop Street, Pittsburgh, PA 15213, USA.
Biomech Model Mechanobiol. 2004 Jun;2(4):239-45. doi: 10.1007/s10237-004-0041-z. Epub 2004 Apr 22.
To understand the role of tendon fibroblast contraction in tendon healing, we investigated the contraction of human patellar tendon fibroblasts (HPTFs) and its regulation by transforming growth factor-beta1 (TGF-beta1), TGF-beta3, and prostaglandin E(2) (PGE(2)). HPTFs were found to wrinkle the underlying thin silicone membranes, demonstrating that these tendon fibroblasts are contractile. Using fibroblast populated collagen gels (FPCGs), exogenous addition of TGF-beta1 or TGF-beta3 was found to increase fibroblast contraction compared to non-treated fibroblasts in serum-free medium, whereas PGE(2) was found to decrease the tendon fibroblast contraction. Moreover, the tendon fibroblasts in collagen gels treated with TGF-beta1 contracted to a greater degree than those treated with TGF-beta3. Since the extent of fibroblast contraction is related to scar tissue formation, this differential effect of TGF-beta1 and TGF-beta3 on HPTF contraction supports the previous finding that TGF-beta1 induces scar tissue formation, whereas TGF-beta3 reduces its formation. Further, the reduced tendon fibroblast contraction by PGE(2) suggests that excessive presence of this inflammatory mediator in the wound site might retard tendon healing. Taken together, the results of this study suggest that regulation of human tendon fibroblast contraction may reduce scar tissue formation and therefore improve the mechanical properties of healing tendons.
为了解肌腱成纤维细胞收缩在肌腱愈合中的作用,我们研究了人髌腱成纤维细胞(HPTFs)的收缩情况以及转化生长因子-β1(TGF-β1)、TGF-β3和前列腺素E2(PGE2)对其的调节作用。我们发现HPTFs能使下方的薄硅胶膜产生褶皱,这表明这些肌腱成纤维细胞具有收缩性。使用成纤维细胞填充的胶原凝胶(FPCGs),发现在无血清培养基中,与未处理的成纤维细胞相比,外源性添加TGF-β1或TGF-β3会增加成纤维细胞的收缩,而PGE2会降低肌腱成纤维细胞的收缩。此外,用TGF-β1处理的胶原凝胶中的肌腱成纤维细胞比用TGF-β3处理的收缩程度更大。由于成纤维细胞收缩的程度与瘢痕组织形成有关,TGF-β1和TGF-β3对HPTF收缩的这种差异作用支持了先前的发现,即TGF-β1诱导瘢痕组织形成,而TGF-β3减少其形成。此外,PGE2导致肌腱成纤维细胞收缩减少,这表明伤口部位这种炎症介质的过量存在可能会阻碍肌腱愈合。综上所述,本研究结果表明,调节人肌腱成纤维细胞的收缩可能会减少瘢痕组织形成,从而改善愈合肌腱的力学性能。