Kartogenin 可诱导软骨祖细胞的软骨生成,并减轻骨髓基质细胞的细胞肥大。

Daniel S Yang, Jay Trivedi, Daniel Betensky, Salomi Desai, Brett D Owens, Chathuraka T Jayasuriya
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引用次数: 0

摘要

简介Kartogenin(KGN)是一种人工合成的小分子化合物,可通过激活smad-4/5通路刺激软骨细胞分化。KGN被认为是昂贵的生物生长因子(如转化生长因子β)的可行替代品,而生物生长因子在患者身上的使用仍受到严格的监管:本研究报告了KGN刺激对软骨间充质祖细胞(CPCs)的影响,这些细胞在基于细胞的肌肉骨骼组织再生应用中被证明是有效的。我们的研究结果表明,KGN处理3-10天后,人CPCs的软骨生成标志物、SOX9和COL2明显增加:结果:KGN 处理也会导致 CPCs 中 GAG 生成量的显著剂量依赖性增加。在人骨髓基质细胞(BM-MSCs)中未观察到同样的疗效;但是,KGN 能显著降低 BM-MSCs 中细胞肥大标志物 COL10 和 MMP13 的 mRNA 表达。与这些mRNA表达结果相同,KGN还能使MMP-13的蛋白水平在KGN处理后的0-5天和5-10天显著下降:总之,本研究表明,KGN 可促进 CPCs 的软骨生成,抑制 BM-MSCs 的肥大终末分化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Kartogenin Induces Chondrogenesis in Cartilage Progenitor Cells and Attenuates Cell Hypertrophy in Marrow-Derived Stromal Cells.

Introduction: Kartogenin (KGN) is a synthetic small molecule that stimulates chondrogenic cellular differentiation by activating smad-4/5 pathways. KGN has been proposed as a feasible alternative to expensive biologic growth factors, such as transforming growth factor β, which remain under strict regulatory scrutiny when it comes to use in patients.

Method: This study reports the previously unexplored effects of KGN stimulation on cartilage- derived mesenchymal progenitor cells (CPCs), which have been shown to be effective in applications of cell-based musculoskeletal tissue regeneration. Our findings demonstrate that KGN treatment significantly increased markers of chondrogenesis, SOX9 and COL2 following 3-10 days of treatment in human CPCs.

Result: KGN treatment also resulted in a significant dose-dependent increase in GAG production in CPCs. The same efficacy was not observed in human marrow-derived stromal cells (BM-MSCs); however, KGN significantly reduced mRNA expression of cell hypertrophy markers, COL10 and MMP13, in BM-MSCs. Parallel to these mRNA expression results, KGN led to a significant decrease in protein levels of MMP-13 both at 0-5 days and 5-10 days following KGN treatment.

Conclusion: In conclusion, this study demonstrates that KGN can boost the chondrogenicity of CPCs and inhibit hypertrophic terminal differentiation of BM-MSCs.

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