Characterized by progressive and irreversible degeneration of the articular cartilage (AC), osteoarthritis (OA) is the most common chronic joint disease, and there is no cure for OA at present. Recent studies suggest that enhancing the recruitment of endogenous mesenchymal stem cells (MSCs) to damaged cartilage is a promising therapeutic strategy for cartilage repair. Tetrahedral framework nucleic acid (tFNA) is a novel DNA nanomaterial and has shown great potential in the field of biomedical science. Transforming growth factor-beta 3 (TGF-β3), a vital member of the highly conserved TGF-β superfamily, is considered to induce chondrogenesis. A 66-base DNA aptamer named HM69 is reported to identify and recruit MSCs. In this study, aptamer HM69-modified tFNAs were successfully self-assembled and used to load TGF-β3 when the disulfide bonds combined. We confirmed the successful synthesis of the final composition, HM69-tFNA@TGF-β3 (HTT), by PAGE, dynamic light scattering, and atomic force microscopy. The results of in vitro experiments showed that HTT effectively induced MSC proliferation, migration, and chondrogenic differentiation. In addition, HTT-treated MSCs were shown to protect the OA chondrocytes. In DMM mice, the injection of HTT improved the therapeutic outcome of mouse pain symptoms and AC degeneration. In conclusion, this study innovatively used the disulfide bonds combined with TGF-β3 and tFNA, and an additional sequence HM69 was loaded on tFNA for the better-targeted recruitment of MSCs. HTT demonstrated its role in promoting the chondrogenesis of MSCs and cartilage protection, indicating that it might be promising for OA therapy.

中文翻译：

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适体修饰的四面体框架核酸与 TGF-β3 协同作用，通过增强 MSC 的软骨分化来促进骨关节炎的软骨保护


骨关节炎（OA）是最常见的慢性关节疾病，以关节软骨（AC）进行性和不可逆的退化为特征，目前尚无治愈方法。最近的研究表明，增强内源性间充质干细胞（MSC）向受损软骨的募集是一种有前途的软骨修复治疗策略。四面体框架核酸（tFNA）是一种新型DNA纳米材料，在生物医学领域显示出巨大的潜力。转化生长因子-β 3 (TGF-β3) 是高度保守的 TGF-β 超家族的重要成员，被认为可以诱导软骨形成。据报道，一种名为 HM69 的 66 碱基 DNA 适体可识别和招募 MSC。在本研究中，适配体HM69修饰的tFNA成功自组装，并在二硫键结合时用于负载TGF-β3。我们通过 PAGE、动态光散射和原子力显微镜证实了最终组合物 HM69-tFNA@TGF-β3 (HTT) 的成功合成。体外实验结果表明，HTT能有效诱导MSC增殖、迁移和成软骨分化。此外，HTT 处理的 MSC 被证明可以保护 OA 软骨细胞。在 DMM 小鼠中，注射 HTT 改善了小鼠疼痛症状和 AC 变性的治疗效果。总之，本研究创新性地使用二硫键结合TGF-β3和tFNA，并在tFNA上加载额外的序列HM69，以更好地靶向招募MSC。 HTT 证明了其在促进 MSC 软骨形成和软骨保护方面的作用，表明它可能有望用于 OA 治疗。