BACKGROUND Meniscal injury is very common, and injured meniscal tissue has a limited healing ability because of poor vascularity. Platelets contain both pro- and anti-angiogenic factors, which can be released by platelet selective activation. HYPOTHESIS Platelets release a high level of vascular endothelial growth factor (VEGF) when they are activated by protease-activated receptor 1 (PAR1), whereas the platelets release endostatin when they are activated by protease-activated receptor 4 (PAR4). The PAR1-treated platelets enhance the proliferation of meniscal cells in vitro and promote in vivo healing of wounded meniscal tissue. STUDY DESIGN Controlled laboratory study. METHOD Platelets were isolated from human blood and activated with different reagents. The released growth factors from the activated platelets were determined by immunostaining and enzyme-linked immunosorbent assay. The effects of the platelets with different treatments on meniscal cells were tested by an in vitro model of cell culture and an in vivo model of wounded meniscal healing. RESULTS The results indicated that platelets contained both pro- and antiangiogenic factors including VEGF and endostatin. In unactivated platelets, VEGF and endostatin were contained inside of the platelets. Both VEGF and endostatin were released from the platelets when they were activated by thrombin. However, only VEGF was released from the platelets when they were activated by PAR1, and only endostatin was released from the platelets when they were activated by PAR4. The rat meniscal cells grew much faster in the medium that contained PAR1-activated platelets than in the medium that contained either PAR4-activated platelets or unactivated platelets. The wounds treated with PAR1-activated platelets healed faster than those treated with either PAR4-activated platelets or unactivated platelets. Many blood vessel-like structures were found in the wounded menisci treated with PAR1-activated platelets. CONCLUSION The PAR1-activated platelets released high levels of VEGF, which increased the proliferation of rat meniscal cells in vitro, enhanced the vascularization of menisci in vivo, and promoted healing of wounded menisci. CLINICAL RELEVANCE Our results suggested that selective activated platelets can be used clinically to enhance healing of wounded meniscal tissue.

中文翻译：

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蛋白酶激活的受体选择性激活的血小板对半月板细胞的差异作用。

背景技术半月板损伤是非常普遍的，并且半月板组织由于血管不良而具有有限的愈合能力。血小板同时含有促血管生成因子和抗血管生成因子，可以通过血小板选择性激活来释放这些因子。假设当血小板被蛋白酶激活的受体1（PAR1）激活时，血小板释放高水平的血管内皮生长因子（VEGF），而当血小板被蛋白酶激活的受体4（PAR4）激活时，血小板释放内皮抑素。PAR1处理的血小板在体外增强半月板细胞的增殖，并促进受伤的半月板组织的体内愈合。研究设计受控的实验室研究。方法从人血中分离血小板，并用不同的试剂活化。通过免疫染色和酶联免疫吸附测定来确定从活化的血小板释放的生长因子。通过细胞培养的体外模型和受伤的半月板愈合的体内模型来测试用不同处理的血小板对半月板细胞的作用。结果结果表明血小板同时含有促血管生成因子和抗血管生成因子，包括VEGF和内皮抑素。在未活化的血小板中，VEGF和内皮抑素被包含在血小板内部。当凝血酶激活时，VEGF和内皮抑素均从血小板中释放出来。但是，当被PAR1激活时，只有VEGF从血小板中释放出来，而当由PAR4激活时，只有内皮抑素从血小板中释放出来。在包含PAR1活化的血小板的培养基中，大鼠半月板细胞的生长比在包含PAR4活化的血小板或未活化的血小板的培养基中生长快得多。用PAR1活化的血小板治疗的伤口比用PAR4活化的血小板或未活化的血小板治疗的伤口愈合更快。在用PAR1活化的血小板治疗的半月板中发现了许多血管样结构。结论PAR1激活的血小板释放高水平的VEGF，从而增加了大鼠半月板细胞的增殖，增强了半月板的体内血管形成，并促进了受伤的半月板的愈合。临床相关性我们的结果表明，选择性活化的血小板可在临床上用于增强受伤的半月板组织的愈合。