Wang Bin, Guo Jia, Feng Lu, Suen Chun-Wai, Fu Wei-Ming, Zhang Jin-Fang, Li Gang
Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China; The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, PR China.
Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China.
Exp Cell Res. 2016 Oct 1;347(2):360-6. doi: 10.1016/j.yexcr.2016.08.018. Epub 2016 Aug 26.
Collagen formation is used as a crucial indicator of tenogenic differentiation of human tendon derived stem cell (hTDSC). Early growth response-1(egr1), a transcriptional factor, has been demonstrated to regulate tendon differentiation and promote tendon repair. Considering that the therapeutic options for tendon injuries remain limited, investigating the regulation of egr1 could facilitate the understanding of tendon development at molecular level so as to find a promising therapeutic target. MicroRNAs (miRNA) have been considered as epigenetic regulators to mediate multiple biological activities including stem cell differentiation. In the present study, biological experiments confirmed the prediction that miR124-3p (miR124) could have direct binding with egr1. We also found that miR124 suppressed collagen formation during the tendon differentiation of hTDSC while anti-miR124 promoted it. Furthermore, egr1 knockdown abolished the promotive effect of anti-miR124, suggesting that miR124 prevents tendon differentiation via suppressing egr1 expression. Therefore, miR124 may be a promising therapeutic target for tendon injury.
胶原蛋白的形成被用作人肌腱衍生干细胞(hTDSC)成腱分化的关键指标。早期生长反应因子1(egr1)作为一种转录因子,已被证明可调节肌腱分化并促进肌腱修复。鉴于肌腱损伤的治疗选择仍然有限,研究egr1的调控机制有助于从分子水平理解肌腱发育,从而找到有前景的治疗靶点。微小RNA(miRNA)被认为是介导包括干细胞分化在内的多种生物学活性的表观遗传调节因子。在本研究中,生物学实验证实了miR124-3p(miR124)可与egr1直接结合的预测。我们还发现,miR124在hTDSC的肌腱分化过程中抑制胶原蛋白的形成,而抗miR124则促进其形成。此外,敲低egr1消除了抗miR124的促进作用,表明miR124通过抑制egr1表达来阻止肌腱分化。因此,miR124可能是肌腱损伤有前景的治疗靶点。