Platelet-released supernatants increase migration and proliferation, and decrease osteogenic differentiation of bone marrow-derived mesenchymal progenitor cells under in vitro conditions
Platelet-released supernatants increase migration and proliferation, and decrease osteogenic differentiation of bone marrow-derived mesenchymal progenitor cells under in vitro conditions
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DOI：
10.1080/09537100310001643999
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发表时间：
2004-02-01
期刊：
影响因子：
3.3
通讯作者：
Watzek, G
中科院分区：
文献类型：
--
作者：
Gruber, R;Karreth, F;Watzek, G
目前，富血小板血浆被推广用作骨移植物的佐剂，以提高新形成骨的数量和质量;然而，其潜在的细胞机制尚未完全了解。我们发现，在体外条件下，去除白细胞的凝血酶活化血小板的上清液增加了骨髓间充质祖细胞的迁移和增殖，并降低了其成骨分化。使用针对血小板衍生生长因子（PDGF）产生的中和抗体，血小板释放上清液的观察到的作用减弱。当细胞外信号调节蛋白激酶（ERK）信号被PD 98059抑制时，促有丝分裂反应也降低;然而，PD 98059并不能逆转血小板释放上清液对迁移和成骨分化的影响。与ERK介导的促有丝分裂活性一致，血清饥饿的间充质祖细胞与血小板释放的上清液孵育增加了激酶的磷酸化。总之，这些观察结果表明，PDGF是血小板活化后释放的关键因子，其可以增加迁移和增殖，并降低体外条件下间充质祖细胞的成骨分化。结果进一步表明，ERK信号转导介导的促有丝分裂反应血小板释放的上清液。
Platelet-rich plasma is currently promoted to serve as an adjuvant for bone grafts to enhance quantity and quality of newly forming bone; however, the underlying cellular mechanisms are not fully understood. We show here that supernatants of leukocyte-depleted thrombin-activated platelets increase migration and proliferation, and decrease osteogenic differentiation of bone marrow-derived mesenchymal progenitor cells under in vitro conditions. Using neutralizing antibodies raised against platelet-derived growth factor (PDGF), the observed effects of platelet-released supernatants were diminished. The mitogenic response was also decreased when extracellular signal-regulated protein kinase (ERK) signalling was inhibited by PD98059; however, PD98059 did not reverse the effects of platelet-released supernatants on migration and osteogenic differentiation. Consistent with an ERK-mediated mitogenic activity, incubation of serum-starved mesenchymal cell progenitors with platelet-released supernatants increased phosphorylation of the kinase. Together, these observations indicate that PDGF is a key factor released upon platelet activation that can increase migration and proliferation, and decreases osteogenic differentiation of mesenchymal progenitor cells under in vitro conditions. The results further suggest that ERK signalling is required to mediate the mitogenic response to platelet-released supernatants.