Anti-osteosarcoma property of decorin-modified titanium surface: A novel strategy to inhibit oncogenic potential of osteosarcoma cells
Anti-osteosarcoma property of decorin-modified titanium surface: A novel strategy to inhibit oncogenic potential of osteosarcoma cells
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核心蛋白聚糖修饰钛表面的抗骨肉瘤特性：抑制骨肉瘤细胞致癌潜力的新策略
DOI：
10.1016/j.biopha.2020.110034
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发表时间：
2020
影响因子：
7.5
通讯作者：
Wang Kun
中科院分区：
文献类型：
--
作者：
Xiao Dahai;Lu Yunxiang;Zhu Lei;Liang Tangzhao;Wang Zhe;Ren Jianhua;He Ronghan;Wang Kun
骨肉瘤是青少年中最常见的骨肉瘤。Decorin （DCN）被认为是一种新的抗骨肉瘤治疗策略。本研究通过多多巴胺（DOPA）在钛（Ti）表面加载装饰素作为锚点，增强骨整合。在这项研究中，我们研究了装饰素包被的Ti底物（Ti - dopa - dcn）对骨肉瘤细胞SAOS-2的致癌潜能的影响。底物置于24孔板中进行细胞培养。采用细胞计数试剂盒-8 （CCK8）法测定细胞活力。DAPI染色和Annexin V-FITC/PI双染色分析细胞凋亡情况。流式细胞术分析细胞周期。Transwell法检测细胞迁移和侵袭。共培养时，将成骨前细胞MEC3T3-E1和骨肉瘤细胞SAOS-2用细胞膜荧光染料染色，并按1:1比例混合共培养。在24、48、72、96 h四个时间点荧光显微镜下观察细胞。结果表明，TI-DOPA-DCN底物可选择性抑制骨肉瘤细胞的增殖，但对成骨前细胞无抑制作用。然而，TI-DOPA-DCN底物不影响SAOS-2的细胞周期。DAPI染色和Annexin V-FITC/PI双染色分析显示，TI-DOPA-DCN底物诱导骨肉瘤细胞凋亡。Transwell实验显示，TI-DOPA-DCN底物抑制骨肉瘤细胞的侵袭和迁移。此外，TI-DOPA-DCN底物在共培养系统中抑制骨肉瘤细胞的生长，但促进成骨前细胞的生长。综上所述，Ti表面的decorin涂层在抑制骨肉瘤细胞的致癌潜能的同时，促进了成骨前细胞的生长，可用于Ti骨科植入物的表面修饰。
Osteosarcoma is the most common bone sarcoma in adolescents. Decorin (DCN) has been proposed to be a new anti-osteosarcoma therapeutic strategy. Our previous study has loaded decorin on titanium (Ti) surface by polydopamine (DOPA) as an anchor to enhance osseointegration. In this study, we investigated the effect of decorin-coated Ti substrates (TI-DOPA-DCN) on the oncogenic potential of osteosarcoma cells SAOS-2. The substrates were placed in 24-well plates for cell culture. Cell viability was determined by Cell Counting Kit-8 (CCK8) assay. Apoptosis was evaluated by DAPI staining and Annexin V-FITC/PI double staining analysis. Cell cycle was analyzed by flow cytometry. Cell migration and invasion were evaluated by Transwell assay. For co-culture, the pre-osteogenic cells MEC3T3-E1 and osteosarcoma cells SAOS-2 were stained with cell membrane fluorescent dyes, and then mixed (1:1) for co-culture. The cells were observed under a fluorescence microscope at four time points of 24, 48, 72, and 96 h. The results showed that TI-DOPA-DCN substrate can selectively inhibit cell proliferation of osteosarcoma cells but not pre-osteoblasts. However, the cell cycle of SAOS-2 was not affected by TI-DOPA-DCN substrates. Both DAPI staining and Annexin V-FITC/PI double staining analysis revealed that TI-DOPA-DCN substrates induced apoptosis of osteosarcoma cells. Transwell assay showed that TI-DOPA-DCN substrates inhibited invasion and migration of osteosarcoma cells. Moreover, TI-DOPA-DCN substrates inhibited the growth of osteosarcoma cells but promoted that of pre-osteoblasts in the coculture system. Taken together, these findings suggested that decorin coating on Ti surface simultaneously inhibited the oncogenic potential of osteosarcoma cells but enhanced cell growth of pre-osteoblasts, which could be applied to surface modification of Ti orthopedic implant.