The distribution of vascular endothelial growth factor in human meniscus and a meniscal injury model

The distribution of vascular endothelial growth factor in human meniscus and a meniscal injury model
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DOI:
10.1016/j.jos.2017.02.006
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发表时间:
2017-07-01
影响因子:
1.7
通讯作者:
Ozaki, Toshifumi
Ozaki, Toshifumi
中科院分区:
医学4区
文献类型:
--
作者:
Lu, Zhichao;Furumatsu, Takayuki;Ozaki, Toshifumi

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背景:半月板在控制膝关节复杂的生物力学方面发挥着重要作用。半月板损伤常见于膝关节。半月板周围毛细血管丛供应外半月板,而内半月板由无血管组织组成。血管生成因子,例如血管内皮生长因子(VEGF),在促进各种组织的血管化中具有重要作用。 VEGF介导的新生血管形成有利于受伤组织的愈合。然而,VEGF 在半月板和损伤半月板中的分布和血管生成作用仍不清楚。我们推测VEGF可以影响半月板细胞并调节半月板愈合过程。方法:半月板取自全膝关节置换术患者。半月板损伤是通过显微手术刀片在体外造成的。分别采用聚合酶链式反应和免疫组化检测VEGF mRNA和蛋白表达。结果:在天然半月板组织中,未检测到VEGF和HIF-1αmRNA的表达。然而,在培养的半月板细胞中发现了 VEGF 和 HIF-1 α mRNA(VEGF:外部 > 内部;HIF-1 α:外部 = 内部)。损伤增加了 VEGF 和 HIF-1 α 的 mRNA 水平,其中外部区域增加幅度最大。免疫组织化学分析显示,VEGF蛋白主要在半月板的外部区域和损伤区域周围检测到。然而,内部和外部半月板来源的介质之间的 VEGF 浓度相似。结论:这项研究表明,半月板的内部和外部区域都含有 VEGF。受伤的半月板组织中 HIF-1 α 表达和 VEGF 沉积较高。我们的结果表明,损伤刺激了 HIF-1a 和 VEGF 的表达,它们可能保留在细胞外基质中,作为受损半月板(尤其是外半月板)的愈合刺激剂。 (C) 2017 年日本骨科协会。由 Elsevier B.V. 出版。保留所有权利。
Background: The meniscus plays an important role in controlling the complex biomechanics of the knee. Meniscus injury is common in the knee joint. The perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Angiogenesis factors, such as vascular endothelial growth factor (VEGF), have important roles in promoting vascularization of various tissues. VEGF-mediated neovascularization is beneficial to the healing of injured tissues. However, the distribution and angiogenic role of VEGF remains unclear in the meniscus and injured meniscus. We hypothesized that VEGF could affect meniscus cells and modulate the meniscus healing process.Methods: Menisci were obtained from total knee arthroplasty patients. Meniscal injury was created ex vivo by a microsurgical blade. VEGF mRNA and protein expression were detected by the polymerase chain reaction and immunohistochemical analyses, respectively.Results: In native meniscal tissue, the expression of VEGF and HIF-1 alpha mRNAs could not be detected. However, VEGF and HIF-1 alpha mRNAs were found in cultured meniscal cells (VEGF: outer > inner; HIF-1 alpha: outer = inner). Injury increased mRNA levels of both VEGF and HIF-1 alpha, with the increase being greatest in the outer area. Immunohistochemical analyses revealed that VEGF protein was detected mainly in the outer region and around injured areas of the meniscus. However, VEGF concentrations were similar between inner and outer menisci-derived media.Conclusions: This study demonstrated that both the inner and outer regions of the meniscus contained VEGF. HIF-1 alpha expression and VEGF deposition were high in injured meniscal tissue. Our results suggest that injury stimulates the expression of HIF-1a and VEGF that may be preserved in the extracellular matrix as the healing stimulator of damaged meniscus, especially in the outer meniscus. (C) 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.