Locally applied angiogenic factors -: A new therapeutic tool for meniscal repair
Locally applied angiogenic factors -: A new therapeutic tool for meniscal repair
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DOI：
10.1016/j.aanat.2005.04.010
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发表时间：
2005-11-01
影响因子：
2.2
通讯作者：
Tillmann, B
中科院分区：
文献类型：
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作者：
Petersen, W;Pufe, T;Tillmann, B
由于中央的三分之二是无血管的，所以在中央的泪囊周围的泪囊比中央的泪囊有更好的加热潜力。半月板的无血管状态通过抗血管生成因子如内皮抑制素的表达来维持。内皮抑素在血管内皮的分布与血管化程度相关。内皮抑素免疫染色在无血管区较强，在血管化的外三分之一减少。内皮抑素与血管内皮细胞的信号转导相互作用。通过减少VEGF诱导的激酶（Erk 1/2）磷酸化来抑制VEGF。VEGF在胎儿半月板血管生成中起重要作用，在成人半月板中表达下调。血管生成因子VEGF的应用。为了评价这一假设，在内侧无血管区创建了一处撕裂。18只美利奴羊半月板。然后用无涂层缝线（组1）、PDLLA涂层缝线（组2）和PDLLA/VEGF涂层缝线（组3）修复撕裂。6周后，我们观察到VEGF治疗组中因子VIII免疫染色增加。然而，在该治疗组（VEGF/PDLLA）中，没有半月板加热。在无涂层缝线组和PDLLA涂层缝线组中，分别在3只动物中观察到部分加热和3只动物中观察到完全加热。因子VIII的表达通常限于血管内皮细胞。然而，在这项研究中，单个内皮细胞。VEGF/PDLLA组的血管壁内可见少量细胞。这一发现表明，VEGF的应用可能刺激血管内皮细胞的增殖，但VEGF的应用是不成功的，在刺激更复杂的过程vasculogenesis.Further免疫组化检查的标本显示，在VEGF/PDLLA组有很强的免疫染色对基质金属蛋白酶13（MMP-13）。体外研究表明，VEGF可以刺激软骨细胞增殖，但也可以通过HIF 1-α诱导表达MMP-13。由于尿道纤维软骨细胞表达VEGF受体2（KDR），MMP表达的诱导可能是另一个抑制愈合的因素，尽管增加了血管生成。总之，通过PDLLA涂层缝线局部应用VEGF不会促进尿道加热。单一的生长因子可能并不总是一个有前途的工具，促进组织修复。进一步的研究必须找出是否生长因子组合（VEGF和血管生成素）可能更有效地刺激血管生成在尿道加热。(c)2005年Elsevier GmbH。All rights reserved.
Tears in the peripheral part of the menisci have a better heating potential than tears in the central part, because the central two-thirds of the menisci are avascular. The avascular status of the meniscus is maintained by the expression of antiangiogenic factors such as endostatin. The distribution of endostatin in the menisci correlates with the degree of vascularization. Endostatin immunostaining is strong in the avascular zone and reduced in the vascularized outer one-third. Endostatin interacts with signal transduction of the vascular endothetial. growth factor (VEGF) by reducing VEGF-induced kinase (Erk1/2) phosphorylation. VEGF plays an important role in angiogenesis in fetal menisci and it is down-regulated in the adult meniscus.We hypothesized that heating of meniscal tears in the avascular zone can be promoted by the local. application of the angiogenic factor VEGF. To evaluate this hypothesis a tear was created in the avascular zone of the medial. meniscus in 18 merino sheep. The tear was then repaired with an uncoated suture (group 1), a suture coated with PDLLA (group 2), and by a suture coated with PDLLA/VEGF (group 3).After 6 weeks we observed increased factor VIII immunostaining in the VEGF-treated group. However, in this treatment group (VEGF/PDLLA) no meniscus heated. In the uncoated suture group and in the PDLLA-coated suture group partial heating was observed in three animals and complete heating in three animals, respectively. Factor VIII expression is normally restricted to vascular endothelial cells. In this study, however, single endothelial. cells could be detected in the menisci of the VEGF/PDLLA group. This finding suggests that the application of VEGF might have stimulated proliferation of vascular endothelial cells but the application of VEGF was not successful in stimulating the more complex process of vasculogenesis.Further immunohistochemical examinations of the specimen have shown that in the VEGF/PDLLA group there is strong immunostaining against matrix metalloproteinase 13 (MMP-13). In vitro studies have shown that VEGF can stimulate chondrocytes to proliferate but also to express MMP-13 via HIF1-alpha induction. Since meniscal fibrochondrocytes express the VEGF receptor 2 (KDR) the induction of MMP expression might be another factor which inhibits healing despite increased angiogenesis.In conclusion, the local application of VEGF via PDLLA-coated sutures does not promote meniscal heating. A single growth factor might not always be a promising tool for the promotion of tissue repair. Further studies have to find out if growth factor combinations (VEGF and angiopoitin) might be more effective in stimulating vasculogenesis during meniscal heating. (c) 2005 Elsevier GmbH. All rights reserved.