Department of Physical and Rehabilitation Medicine, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
R&D Center, ENCell Co. Ltd., Seoul 06072, Korea.
Int J Mol Sci. 2020 Apr 13;21(8):2687. doi: 10.3390/ijms21082687.
The inhibition of the aberrant differentiation of tendon-derived stem cells (TDSCs) is a major target for the regeneration of damaged tendon tissues, as tendinopathy can be caused by the aberrant differentiation of TDSCs. We investigated whether the possible aberrant differentiation of TDSCs can be prevented by using adequate inhibitors. TDSCs extracted from chemically induced tendinopathy and injury-with-overuse tendinopathy models were cultured with 18α-glycyrrhetinic acid (AGA) and T0070907 to block osteogenic differentiation and adipogenic differentiation, respectively. The optimal dose of AGA decreased the osteogenic-specific marker Runx2 (Runt-related transcription factor 2), and T0070907 blocked the adipogenic-specific marker peroxisome proliferator-activated receptor gamma (PPARγ) in mRNA levels. We also found that AGA induced tenogenic differentiation in mRNA levels. However, T0070907 did not affect the tenogenic differentiation and regenerative capacity of TDSCs. We expect that optimal doses of AGA and T0070907 can prevent tendinopathy by inhibiting osteogenic and adipogenic differentiation, respectively. In addition, AGA and T0070907 may play important roles in the treatment of tendinopathy.
抑制肌腱衍生干细胞（TDSCs）的异常分化是损伤性肌腱组织再生的主要目标，因为肌腱病可能是由 TDSCs 的异常分化引起的。我们研究了是否可以使用适当的抑制剂来防止 TDSCs 的异常分化。使用 18α-甘草次酸（AGA）和 T0070907 分别阻断成骨分化和脂肪分化，培养从化学诱导的肌腱病和过度使用性损伤模型中提取的 TDSCs。AGA 的最佳剂量降低了成骨特异性标志物 Runt 相关转录因子 2（Runx2）的 mRNA 水平，而 T0070907 阻断了脂肪特异性标志物过氧化物酶体增殖物激活受体γ（PPARγ）的 mRNA 水平。我们还发现 AGA 诱导了 TDSCs 在 mRNA 水平上的腱形成分化。然而，T0070907 并不影响 TDSCs 的腱形成分化和再生能力。我们期望 AGA 和 T0070907 的最佳剂量可以通过抑制成骨和脂肪分化来分别预防肌腱病。此外，AGA 和 T0070907 可能在肌腱病的治疗中发挥重要作用。
