Park Jin-Ho, Park Bong-Wook, Kang Young-Hoon, Byun Sung-Hoon, Hwang Sun-Chul, Kim Deok Ryong, Woo Dong Kyun, Byun June-Ho
Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju, South Korea.
Department of Orthopaedic Surgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, South Korea.
Cell Biochem Funct. 2017 Dec;35(8):497-509. doi: 10.1002/cbf.3305. Epub 2017 Nov 16.
Despite a capacity for proliferation and an ability to differentiate into multiple cell types, in long-term culture and with ageing, stem cells show a reduction in growth, display a decrease in differentiation potential, and enter senescence without evidence of transformation. The Lin28a gene encodes an RNA-binding protein that plays a role in regulating stem cell activity, including self-renewal and differentiation propensity. However, the effect of the Lin28a gene on cultured human osteoprecursor cells is poorly understood. In the present study, alkaline phosphatase activity, alizarin red-positive mineralization, and calcium content, positive indicators of osteogenic differentiation, were significantly higher in cultured human periosteum-derived cells (hPDCs) with Lin28a overexpression compared with cells without Lin28a overexpression. Lin28a overexpression by hPDCs also increased mitochondrial activity, which is essential for cellular proliferation, as suggested by a reduced presence of reactive oxygen species and significantly enhanced lactate levels and ATP production. Our results suggest that, in hPDCs, the Lin28a gene enhances osteoblastic differentiation and increases mitochondrial activity. Although Lin28a is known as a marker of undifferentiated human embryogenic stem cell, there is limited evidence regarding the influence of Lin28a on osteoblastic differentiation of cultured osteoprecursor cells. This study was to examine the impact of Lin28a on osteogenic phenotypes of human periosteum-derived cells. Their phenotypes can be similar to those of mesenchymal stem cells. Our results suggest that the Lin28a gene enhances the osteoblastic differentiation of human periosteum-derived cells. In addition, the Lin28a gene increases mitochondrial activity in human periosteum-derived cells.
尽管干细胞具有增殖能力并能够分化为多种细胞类型，但在长期培养和衰老过程中，干细胞的生长会减少，分化潜能会降低，并进入衰老状态，且无转化迹象。Lin28a基因编码一种RNA结合蛋白，该蛋白在调节干细胞活性（包括自我更新和分化倾向）中发挥作用。然而，Lin28a基因对培养的人骨前体细胞的影响尚不清楚。在本研究中，与未过表达Lin28a的细胞相比，过表达Lin28a的培养人骨膜来源细胞（hPDCs）中，成骨分化的阳性指标——碱性磷酸酶活性、茜素红阳性矿化和钙含量显著更高。hPDCs过表达Lin28a还增加了线粒体活性，这对细胞增殖至关重要，这表现为活性氧的存在减少以及乳酸水平和ATP产量显著提高。我们的结果表明，在hPDCs中，Lin28a基因增强了成骨细胞分化并增加了线粒体活性。尽管Lin28a被认为是未分化的人胚胎干细胞的标志物，但关于Lin28a对培养的骨前体细胞成骨分化影响的证据有限。本研究旨在研究Lin28a对人骨膜来源细胞成骨表型的影响。它们的表型可能与间充质干细胞的表型相似。我们的结果表明，Lin28a基因增强了人骨膜来源细胞的成骨细胞分化。此外，Lin28a基因增加了人骨膜来源细胞的线粒体活性。
