Department of Oral Biotechnology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
Faculty of Biology, University of Freiburg, Freiburg, Germany.
J Bone Miner Metab. 2019 Jan;37(1):105-117. doi: 10.1007/s00774-017-0900-1. Epub 2018 Jan 11.
In our previous study, we revealed significant differences of osteopontin (OPN) gene expression in primary human osteoblasts (HOBs) derived from iliac crest bone (iHOBs) and alveolar bone (aHOBs). The present study aims at assigning this discriminative expression to a possible biologic function. OPN is known to be involved in several pathologic and physiologic processes, among others angiogenesis. Therefore, we studied the reaction of human umbilical vein endothelial cells (HUVECs) to HOB-derived OPN regarding angiogenesis. To this end, human primary explant cultures of both bone entities from ten donors were established. Subsequent transcription analysis detected higher gene expression of OPN in iHOBs compared to aHOBs, thereby confirming the results of our previous study. This difference was particularly apparent when cultures were derived from female donors. Hence, OPN protein expression as well as the angiogenic potential of OPN was analyzed, originating from HOBs of one female donor. In accordance to the gene expression level, secreted OPN was more abundant in the supernatant of iHOBs than in aHOBs. Moreover, secreted OPN was found to stimulate migration of HUVECs, but not proliferation or tube formation. These results indicate an involvement in very early stages of angiogenesis and a functional distinction of OPN from HOBs derived from different bone entities.
在我们之前的研究中,我们揭示了源自髂嵴骨(iHOB)和牙槽骨(aHOB)的原代人成骨细胞(HOB)中骨桥蛋白(OPN)基因表达的显著差异。本研究旨在将这种有区别的表达归因于可能的生物学功能。已知 OPN 参与了几种病理和生理过程,包括血管生成。因此,我们研究了人脐静脉内皮细胞(HUVEC)对源自 HOB 的 OPN 的血管生成反应。为此,我们从十个供体建立了两种骨实体的人原代外植体培养物。随后的转录分析检测到 iHOB 中 OPN 的基因表达高于 aHOB,从而证实了我们之前的研究结果。当培养物源自女性供体时,这种差异尤其明显。因此,我们分析了源自一位女性供体的 HOB 的 OPN 蛋白表达和血管生成潜能。与基因表达水平一致,iHOB 上清液中分泌的 OPN 比 aHOB 中更丰富。此外,发现分泌的 OPN 可刺激 HUVEC 的迁移,但不能刺激增殖或管形成。这些结果表明 OPN 参与了血管生成的非常早期阶段,并显示出源自不同骨实体的 HOB 的功能区别。