Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy.
Department of Internal Medicine (DIMI), University of Genova, 16132 Genova, Italy.
Int J Mol Sci. 2020 Jul 20;21(14):5123. doi: 10.3390/ijms21145123.
To understand the regenerative effect of platelet-released molecules in bone repair one should investigate the cascade of events involving the resident osteoblast population during the reconstructive process. Here the in vitro response of human osteoblasts to a platelet lysate (PL) stimulus is reported. Quiescent or very slow dividing osteoblasts showed a burst of proliferation after PL stimulation and returned to a none or very slow dividing condition when the PL was removed. PL stimulated osteoblasts maintained a differentiation capability in vitro and in vivo when tested in absence of PL. Since angiogenesis plays a crucial role in the bone healing process, we investigated in PL stimulated osteoblasts the activation of hypoxia-inducible factor 1-alpha (HIF-1α) and signal transducer and activator of transcription 3 (STAT3) pathways, involved in both angiogenesis and bone regeneration. We observed phosphorylation of STAT3 and a strong induction, nuclear translocation and DNA binding of HIF-1α. In agreement with the induction of HIF-1α an enhanced secretion of vascular endothelial growth factor (VEGF) occurred. The double effect of the PL on quiescent osteoblasts, i.e., resumption of proliferation and activation of pathways promoting both angiogenesis and bone formation, provides a rationale to the application of PL as therapeutic agent in post-traumatic bone repair.
为了理解血小板释放分子在骨修复中的再生作用，人们应该研究在重建过程中涉及常驻成骨细胞群体的一系列事件。本文报道了人成骨细胞对血小板裂解液（PL）刺激的体外反应。静止或分裂缓慢的成骨细胞在 PL 刺激后会爆发性增殖，当 PL 被去除时，又恢复到非分裂或非常缓慢分裂的状态。在没有 PL 的情况下进行测试时，PL 刺激的成骨细胞在体外和体内均保持分化能力。由于血管生成在骨愈合过程中起着至关重要的作用，我们研究了 PL 刺激的成骨细胞中缺氧诱导因子 1-α（HIF-1α）和信号转导和转录激活因子 3（STAT3）途径的激活，这些途径涉及血管生成和骨再生。我们观察到 STAT3 的磷酸化以及 HIF-1α 的强烈诱导、核易位和 DNA 结合。与 HIF-1α 的诱导一致，血管内皮生长因子（VEGF）的分泌增加。PL 对静止成骨细胞的双重作用，即恢复增殖和激活促进血管生成和骨形成的途径，为 PL 作为创伤后骨修复治疗剂的应用提供了依据。
