Cutarelli Alessandro, Marini Mario, Tancredi Virginia, D'Arcangelo Giovanna, Murdocca Michela, Frank Claudio, Tarantino Umberto
Department of Orthopaedics and Traumatology, University Hospital Foundation, Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy.
National Centre for Rare Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, 00161, Italy.
Dev Growth Differ. 2016 May;58(4):400-8. doi: 10.1111/dgd.12288. Epub 2016 May 18.
In the last years adenosine triphosphate (ATP) and subsequent purinergic system activation through P2 receptors were investigated highlighting their pivotal role in bone tissue biology. In osteoblasts ATP can regulate several activities like cell proliferation, cell death, cell differentiation and matrix mineralization. Since controversial results exist, in this study we analyzed the ATP effects on differentiation and mineralization in human osteoblast-like Saos-2 cells. We showed for the first time the altered functional activity of ATP receptors. Despite that, we found that ATP can reduce cell proliferation and stimulate osteogenic differentiation mainly in the early stages of in vitro maturation as evidenced by the enhanced expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2) and Osteocalcin (OC) genes and by the increased ALP activity. Moreover, we found that ATP can affect mineralization in a biphasic manner, at low concentrations ATP always increases mineral deposition while at high concentrations it always reduces mineral deposition. In conclusion, we show the osteogenic effect of ATP on both early and late stage activities like differentiation and mineralization, for the first time in human osteoblastic cells.
在过去几年中，人们对三磷酸腺苷（ATP）以及随后通过P2受体激活的嘌呤能系统进行了研究，突出了它们在骨组织生物学中的关键作用。在成骨细胞中，ATP可以调节多种活动，如细胞增殖、细胞死亡、细胞分化和基质矿化。由于存在相互矛盾的结果，在本研究中，我们分析了ATP对人成骨样Saos-2细胞分化和矿化的影响。我们首次展示了ATP受体功能活性的改变。尽管如此，我们发现ATP主要在体外成熟的早期阶段可以减少细胞增殖并刺激成骨分化，碱性磷酸酶（ALP）、Runt相关转录因子2（Runx2）和骨钙素（OC）基因表达增强以及ALP活性增加证明了这一点。此外，我们发现ATP可以以双相方式影响矿化，低浓度时ATP总是增加矿物质沉积，而高浓度时它总是减少矿物质沉积。总之，我们首次在人成骨细胞中展示了ATP对分化和矿化等早期和晚期活动的成骨作用。
