Transforming growth factor-beta stimulates human bone marrow-derived mesenchymal stem/stromal cell chondrogenesis more so than kartogenin
Transforming growth factor-beta stimulates human bone marrow-derived mesenchymal stem/stromal cell chondrogenesis more so than kartogenin
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DOI：
10.1038/s41598-020-65283-8
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发表时间：
2020-05-20
影响因子：
4.6
通讯作者：
Doran, M. R.
中科院分区：
文献类型：
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作者：
Music, E.;Klein, T. J.;Doran, M. R.
先前的研究确定Kartogenin（KGN）是骨髓间充质干细胞/基质细胞（BMSC）软骨形成的有效调节剂。这份最初的报告没有将KGN与转化生长因子-β 1（TGF-β 1）直接进行对比，TGF-β 1是软骨诱导培养基中最常用的生长因子。在此，我们使用高分辨率微粒模型系统直接比较了TGF-β 1和KGN的体外软骨形成效力。将微团在补充有TGF-β 1、KGN或TGF-β 1+KGN两者的培养基中培养7-14天。在诱导14天后，暴露于单独的TGF-β 1或TGF-β 1+KGN组合的微团比仅KGN培养物更大并且产生更多的糖胺聚糖（GAG）。当使用TGF-β 1+KGN时，GAG量与仅TGF-β 1培养物相似或略高，这取决于BMSC供体。单独补充KGN的BMSC微团培养物在培养期间尺寸收缩，并产生最小的GAG。在TGF-β 1+KGN培养物中，肥大的指标没有减轻，表明KGN不阻碍BMSC肥大。相对于TGF-β 1，KGN似乎在人BMSC培养物中具有弱的软骨形成能力，不阻碍肥大，并且可能不是软骨组织工程中生长因子的可行替代品。
A previous study identified kartogenin (KGN) as a potent modulator of bone marrow mesenchymal stem/stromal cell (BMSC) chondrogenesis. This initial report did not contrast KGN directly against transforming growth factor-beta 1 (TGF-beta 1), the most common growth factor used in chondrogenic induction medium. Herein, we directly compared the in vitro chondrogenic potency of TGF-beta 1 and KGN using a high resolution micropellet model system. Micropellets were cultured for 7-14 days in medium supplemented with TGF-beta 1, KGN, or both TGF-beta 1+KGN. Following 14 days of induction, micropellets exposed to TGF-beta 1 alone or TGF-beta 1+KGN in combination were larger and produced more glycosominoglycan (GAG) than KGN-only cultures. When TGF-beta 1+KGN was used, GAG quantities were similar or slightly greater than the TGF-beta 1-only cultures, depending on the BMSC donor. BMSC micropellet cultures supplemented with KGN alone contracted in size over the culture period and produced minimal GAG. Indicators of hypertrophy were not mitigated in TGF-beta 1+KGN cultures, suggesting that KGN does not obstruct BMSC hypertrophy. KGN appears to have weak chondrogenic potency in human BMSC cultures relative to TGF-beta 1, does not obstruct hypertrophy, and may not be a viable alternative to growth factors in cartilage tissue engineering.