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Comparative Analysis of Tenogenic Gene Expression in Tenocyte-Derived Induced Pluripotent Stem Cells and Bone Marrow-Derived Mesenchymal Stem Cells in Response to Biochemical and Biomechanical Stimuli
Stem Cells International ( IF 4.3 ) Pub Date : 2021-01-15 , DOI: 10.1155/2021/8835576 Feikun Yang 1 , Dean W. Richardson 1
Stem Cells International ( IF 4.3 ) Pub Date : 2021-01-15 , DOI: 10.1155/2021/8835576 Feikun Yang 1 , Dean W. Richardson 1
Affiliation
The tendon is highly prone to injury, overuse, or age-related degeneration in both humans and horses. Natural healing of injured tendon is poor, and cell-based therapeutic treatment is still a significant clinical challenge. In this study, we extensively investigated the expression of tenogenic genes in equine bone marrow mesenchymal stem cells (BMSCs) and tenocyte-derived induced pluripotent stem cells (teno-iPSCs) stimulated by growth factors (TGF-β3 and BMP12) combined with ectopic expression of tenogenic transcription factor MKX or cyclic uniaxial mechanical stretch. Western blotting revealed that TGF-β3 and BMP12 increased the expression of transcription factors SCX and MKX in both cells, but the tenocyte marker tenomodulin (TNMD) was detected only in BMSCs and upregulated by either inducer. On the other hand, quantitative real-time PCR showed that TGF-β3 increased the expression of EGR1, COL1A2, FMOD, and TNC in BMSCs and SCX, COL1A2, DCN, FMOD, and TNC in teno-iPSCs. BMP12 treatment elevated SCX, MKX, DCN, FMOD, and TNC in teno-iPSCs. Overexpression of MKX increased SCX, DCN, FMOD, and TNC in BMSCs and EGR1, COL1A2, DCN, FMOD, and TNC in teno-iPSCs; TGF-β3 further enhanced TNC in BMSCs. Moreover, mechanical stretch increased SCX, EGR1, DCN, ELN, and TNC in BMSCs and SCX, MKX, EGR1, COL1A2, DCN, FMOD, and TNC in teno-iPSCs; TGF-β3 tended to further elevate SCX, ELN, and TNC in BMSCs and SCX, MKX, COL1A2, DCN, and TNC in teno-iPSCs, while BMP12 further uptrended the expression of SCX and DCN in BMSCs and DCN in teno-iPSCs. Additionally, the aforementioned tenogenic inducers also affected the expression of signaling regulators SMAD7, ETV4, and SIRT1 in BMSCs and teno-iPSCs. Taken together, our data demonstrate that, in respect to the tenocyte-lineage-specific gene expression, BMSCs and teno-iPSCs respond differently to the tenogenic stimuli, which may affect the outcome of their application in tendon repair or regeneration.
中文翻译:
肌腱细胞诱导的多能干细胞和骨髓间充质干细胞对生化和生物力学刺激的反应中tenogenic基因表达的比较分析。
在人和马中,肌腱极易受伤,过度使用或与年龄有关的变性。受伤的腱的自然愈合很差,基于细胞的治疗仍然是重大的临床挑战。在这项研究中,我们广泛地研究在马骨髓间充质干细胞(BMSC)和肌腱细胞衍生的诱导多能干细胞tenogenic基因的表达(腱的iPSC)刺激由生长因子(TGF- β结合异位3和BMP12)基因转录因子MKX的表达或环状单轴机械拉伸。免疫印迹表明TGF- β图3和BMP12增加了两种细胞中转录因子SCX和MKX的表达,但是仅在BMSC中检测到了肌腱标志物tenomodulin(TNMD),并且由任一诱导物上调。在另一方面,定量实时PCR显示TGF- β 3增加的表达EGR1,COL1A2,FMOD,和TNC在骨髓基质细胞和SCX,COL1A2,DCN,FMOD,和TNC在腱的iPSC。BMP12处理升高了SCX,MKX,DCN,FMOD和TNC在teno-iPSC中。MKX的过表达增加了BMSC中的SCX,DCN,FMOD和TNC以及teno -iPSC中的EGR1,COL1A2,DCN,FMOD和TNC ; TGF- β 3进一步增强TNC在骨髓基质细胞。此外,机械拉伸增加了BMSC和SCX,MKX,EGR1,COL1A2,DCN,FMOD中的SCX,EGR1,DCN,ELN和TNC和teno-iPSC中的TNC;TGF- β 3趋向于进一步提升SCX,ELN和TNC在骨髓基质细胞和SCX,MKX,COL1A2,DCN,和TNC在腱的iPSC,而BMP12进一步uptrended的表达SCX和DCN在骨髓基质细胞和DCN在腱的iPSC 。此外,上述肌腱诱导剂还影响信号调节因子SMAD7,ETV4和SIRT1的表达。在BMSC和teno-iPSC中。综上所述,我们的数据表明,关于肌腱细胞谱系特异性基因表达,BMSC和teno-iPSC对肌腱刺激的反应不同,这可能会影响其在肌腱修复或再生中的应用结果。
更新日期:2021-01-16
中文翻译:
肌腱细胞诱导的多能干细胞和骨髓间充质干细胞对生化和生物力学刺激的反应中tenogenic基因表达的比较分析。
在人和马中,肌腱极易受伤,过度使用或与年龄有关的变性。受伤的腱的自然愈合很差,基于细胞的治疗仍然是重大的临床挑战。在这项研究中,我们广泛地研究在马骨髓间充质干细胞(BMSC)和肌腱细胞衍生的诱导多能干细胞tenogenic基因的表达(腱的iPSC)刺激由生长因子(TGF- β结合异位3和BMP12)基因转录因子MKX的表达或环状单轴机械拉伸。免疫印迹表明TGF- β图3和BMP12增加了两种细胞中转录因子SCX和MKX的表达,但是仅在BMSC中检测到了肌腱标志物tenomodulin(TNMD),并且由任一诱导物上调。在另一方面,定量实时PCR显示TGF- β 3增加的表达EGR1,COL1A2,FMOD,和TNC在骨髓基质细胞和SCX,COL1A2,DCN,FMOD,和TNC在腱的iPSC。BMP12处理升高了SCX,MKX,DCN,FMOD和TNC在teno-iPSC中。MKX的过表达增加了BMSC中的SCX,DCN,FMOD和TNC以及teno -iPSC中的EGR1,COL1A2,DCN,FMOD和TNC ; TGF- β 3进一步增强TNC在骨髓基质细胞。此外,机械拉伸增加了BMSC和SCX,MKX,EGR1,COL1A2,DCN,FMOD中的SCX,EGR1,DCN,ELN和TNC和teno-iPSC中的TNC;TGF- β 3趋向于进一步提升SCX,ELN和TNC在骨髓基质细胞和SCX,MKX,COL1A2,DCN,和TNC在腱的iPSC,而BMP12进一步uptrended的表达SCX和DCN在骨髓基质细胞和DCN在腱的iPSC 。此外,上述肌腱诱导剂还影响信号调节因子SMAD7,ETV4和SIRT1的表达。在BMSC和teno-iPSC中。综上所述,我们的数据表明,关于肌腱细胞谱系特异性基因表达,BMSC和teno-iPSC对肌腱刺激的反应不同,这可能会影响其在肌腱修复或再生中的应用结果。