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Human primary chondrocytes exhibit an anti-angiogenic effect despite of high secretion of VEGF

机译：尽管VEGF高分泌，人原代软骨细胞仍显示抗血管生成作用

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Cartilage tissue is one of the few avascular tissues in humans. This fact suggests that healthy cartilage is capable to prevent the influence of angiogenesis driven by environmental stimuli such as low oxygen partial pressure and changes in pH. The aim of this work was to demonstrate and to quantify the anti-angiogenic potential of normal human chondrocytes in comparison to de-differentiated human chondrocytes and chondrosarcoma cells. We found that conditioned medium of primary human chondrocytes exhibits strong anti-angiogenic properties (inhibition of human umbilical vein endothelial cell proliferation and sprouting). The effect was specific to differentiated chondrocytes, whereas it was absent in conditioned medium from de-differentiated chondrocytes. Furthermore, we revealed that the effect was specifically anti-angiogenic but not generally anti-proliferative, when we compared the effect of the above mentioned conditioned media on proliferation of human umbilical vein endothelial cell versus smooth muscle cell. In addition, we found that the inhibition of HUVEC proliferation caused by conditioned medium of differentiated chondrocyte was even stronger than the anti-proliferative effect of Rapamycin treatment. In contrast, we could demonstrate that conditioned medium of chondrosarcoma cells SW1353 exhibits pro- angiogenic effects. The results from vascular endothelial growth factor ELISA revealed that the inhibition of HUVEC proliferation and sprouting caused by conditioned medium of chondrocytes was not a result of a decreased amount of secreted VEGF. In contrast to our expectations, the results demonstrated that these anti-proliferative effects of conditioned medium of differentiated chondrocytes were present despite of a very high content of VEGF together with other bioactive substances secreted by differentiated chondrocytes. This fact indicates that there might exist potential anti-angiogenic substances secreted by differentiated chondrocytes that are able to overcome the pro-angiogenic effect of VEGF. Such factors might be a very beneficial source as natural anti-angiogeniccompounds bearing minimal side effects.
机译：软骨组织是人类中少数的无血管组织之一。这一事实表明，健康的软骨能够防止由环境刺激（例如低氧分压和pH值变化）驱动的血管生成的影响。这项工作的目的是证明和量化正常人软骨细胞与去分化的人类软骨细胞和软骨肉瘤细胞相比的抗血管生成潜力。我们发现原代人软骨细胞的条件培养基表现出很强的抗血管生成特性（抑制人脐静脉内皮细胞的增殖和发芽）。这种作用对分化的软骨细胞是特异的，而在条件培养基中，去分化的软骨细胞则没有这种作用。此外，当我们比较上述条件培养基对人脐静脉内皮细胞和平滑肌细胞增殖的作用时，我们揭示了该作用特别是抗血管生成的，但通常不是抗增殖的。此外，我们发现，分化软骨细胞条件培养基对HUVEC增殖的抑制作用甚至比雷帕霉素治疗的抗增殖作用更强。相反，我们可以证明软骨肉瘤细胞SW1353的条件培养基表现出促血管生成作用。血管内皮生长因子ELISA的结果表明，软骨细胞条件培养基对HUVEC增殖和发芽的抑制不是由于分泌的VEGF量减少所致。与我们的预期相反，结果表明，尽管VEGF和分化软骨细胞分泌的其他生物活性物质的含量很高，但分化软骨细胞条件培养基的这些抗增殖作用仍然存在。这一事实表明，可能存在分化的软骨细胞分泌的潜在抗血管生成物质，它们能够克服VEGF的促血管生成作用。这些因素可能是非常有益的来源，因为天然抗血管生成化合物的副作用极小。

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