Enhanced Tissue Integration During Cartilage Repair In Vitro Can Be Achieved by Inhibiting Chondrocyte Death at the Wound Edge
Enhanced Tissue Integration During Cartilage Repair In Vitro Can Be Achieved by Inhibiting Chondrocyte Death at the Wound Edge
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DOI：
10.1089/ten.tea.2008.0361
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发表时间：
2009-07-01
影响因子：
4.1
通讯作者：
Archer, Charles W.
中科院分区：
文献类型：
--
作者：
Gilbert, Sophie J.;Singhrao, Sim K.;Archer, Charles W.
目的：实验性关节软骨损伤导致损伤边缘细胞死亡。本研究的目的是探讨抑制这种细胞死亡是否会促进软骨的整体修复。方法：将牛关节软骨(6 Mm)培养在含有坏死(NEC-1)或凋亡抑制物(Z-VAD-FMK，ZVF)的培养液中，然后切割3 mm的内核。将该核心留在原位，形成盘状/环状复合材料，与抑制剂一起培养长达6周，分析细胞死亡、硫酸糖胺聚糖释放和组织整合。结果：创建盘状/环状复合材料导致坏死显著增加。ZVF可显著减少创面边缘的坏死和细胞凋亡。NEC-1减少坏死。这两种抑制剂都能减少创伤引起的糖胺多糖的损失。甲苯胺蓝染色和软骨电子显微镜显示，ZVF处理的圆盘/环复合材料伤口边缘明显整合。NEC-1改善了整合，但程度较小。与对照组相比，ZVF提高了关节软骨的粘接强度。结论：在创伤修复过程中使用细胞死亡抑制剂处理关节软骨，增加了创缘存活细胞的数量，防止了基质丢失，并显著改善了软骨-软骨的整合。
Objective: Experimental wounding of articular cartilage results in cell death at the lesion edge. The objective of this study was to investigate whether inhibition of this cell death results in enhanced integrative cartilage repair.Methods: Bovine articular cartilage discs (6mm) were incubated in media containing inhibitors of necrosis (Necrostatin-1, Nec-1) or apoptosis (Z-VAD-FMK, ZVF) before cutting a 3mm inner core. This core was left in situ to create disc/ring composites, cultured for up to 6 weeks with the inhibitors, and analyzed for cell death, sulfated glycosaminoglycan release, and tissue integration.Results: Creating the disc/ring composites resulted in a significant increase in necrosis. ZVF significantly reduced necrosis and apoptosis at the wound edge. Nec-1 reduced necrosis. Both inhibitors reduced the level of wound-induced sulfated glycosaminoglycan loss. Toluidine blue staining and electron microscopy of cartilage revealed significant integration of the wound edges in disc/ring composites treated with ZVF. Nec-1 improved integration, but to a lesser extent. Push-out testing revealed that ZVF increased adhesive strength compared to control composites.Conclusions: This study shows that treatment of articular cartilage with cell death inhibitors during wound repair increases the number of viable cells at the wound edge, prevents matrix loss, and results in a significant improvement in cartilage-cartilage integration.