Townley W A, Cambrey A D, Khaw P T, Grobbelaar A O
RAFT Institute of Plastic and Reconstructive Surgery, Mount Vernon Hospital, Northwood, UK.
J Hand Surg Eur Vol. 2009 Dec;34(6):783-7. doi: 10.1177/1753193409345188. Epub 2009 Sep 28.
Mechanical tension and contracture are two related facets of tissue biology. This study assessed the effect of ilomastat, a broad-spectrum matrix metalloprotease (MMP) inhibitor, on generation of tension by Dupuytren's disease fibroblasts. Nodule and cord-derived fibroblasts were isolated from five patients with Dupuytren's disease; flexor retinaculum acted as the control. A culture force monitor (CFM) provided an in vitro model of tissue organization to assess development of mechanical tension, lattice contraction and spatial remodelling by fibroblasts. Responses to ilomastat were compared to treatment with a control peptide. Nodule and cord-derived fibroblasts exhibited a two-fold increase in tension compared with flexor retinaculum. Ilomastat significantly inhibited development of tension by nodule and cord but not flexor retinaculum derived fibroblasts at 100 microM. These results imply that MMP activity mediates regulation of tensile strength by Dupuytren's disease fibroblasts and may be an important therapeutic target in patients with Dupuytren's disease.
机械张力和挛缩是组织生物学的两个相关方面。本研究评估了广谱基质金属蛋白酶（MMP）抑制剂伊洛马司他对Dupuytren病成纤维细胞产生张力的影响。从5例Dupuytren病患者中分离出结节和条索来源的成纤维细胞；屈肌支持带作为对照。培养力监测仪（CFM）提供了一个组织构建的体外模型，以评估成纤维细胞产生的机械张力、晶格收缩和空间重塑。将伊洛马司他的反应与对照肽处理进行比较。与屈肌支持带相比，结节和条索来源的成纤维细胞产生的张力增加了两倍。在100微摩尔浓度下，伊洛马司他显著抑制结节和条索来源的成纤维细胞产生张力，但对屈肌支持带来源的成纤维细胞无此作用。这些结果表明，MMP活性介导了Dupuytren病成纤维细胞对拉伸强度的调节，可能是Dupuytren病患者的一个重要治疗靶点。
