Shi Weili, Wu Jiangyi, Pi Yanbin, Yan Xingran, Hu Xiaoqing, Cheng Jin, Yu Huilei, Shao Zhenxing
Peking University Third Hospital, Beijing Key Laboratory of Sports Injuries, Department of Sports Medicine, Institute of Sports Medicine of Peking University, Beijing 100191, China.
Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, China.
Bioengineering (Basel). 2023 Jun 30;10(7):781. doi: 10.3390/bioengineering10070781.
Therapeutic strategies based on utilizing endogenous BMSCs have been developed for the regeneration of bone, cartilage, and ligaments. We previously found that E7 peptide (EPLQLKM) could enhance BMSC homing in bio-scaffolds and, therefore, promote cartilage regeneration. However, the profile and mechanisms of E7 peptide in cartilage regeneration remain elusive. In this study, we examined the effect of E7 peptide on the BMSC phenotype, including adhesion, viability and chondrogenic differentiation, and its underlying mechanism. The konjac glucomannan microsphere (KGM), a carrier material that is free of BMSC adhesion ability, was used as the solid base of E7 peptide to better explore the independent role of E7 peptide in BMSC behavior. The results showed that E7 peptide could support BMSC adhesion and viability in a comparable manner to RGD and promote superior chondrogenic differentiation to RGD. We examined differentially expressed genes of BMSCs induced by E7 compared to RGD. Subsequently, a real-time PCR validated the significantly upregulated expression of lncRNA H19, and the knockdown of lncRNA H19 or miR675, a downstream functional unit of H19, could significantly obscure the chondrogenic differentiation induced by E7. In conclusion, this study confirmed the independent role of E7 in the adhesion and viability of BMSCs and revealed the pro-chondrogenic effect of E7 on BMSCs via the H19/miR675 axis. These results could help establish new therapeutic strategies based on employing endogenous BMSCs for cartilage tissue regeneration.
基于利用内源性骨髓间充质干细胞（BMSCs）的治疗策略已被开发用于骨、软骨和韧带的再生。我们之前发现E7肽（EPLQLKM）可以增强生物支架中BMSCs的归巢能力，从而促进软骨再生。然而，E7肽在软骨再生中的作用概况和机制仍不清楚。在本研究中，我们研究了E7肽对BMSCs表型的影响，包括黏附、活力和软骨分化及其潜在机制。魔芋葡甘露聚糖微球（KGM）是一种没有BMSCs黏附能力的载体材料，被用作E7肽的固体载体，以更好地探索E7肽在BMSCs行为中的独立作用。结果表明，E7肽能够以与RGD相当的方式支持BMSCs的黏附和活力，并促进比RGD更好的软骨分化。我们检测了与RGD相比，E7诱导的BMSCs差异表达基因。随后，实时PCR验证了lncRNA H19的表达显著上调，并且lncRNA H19或其下游功能单元miR675的敲低能够显著削弱E7诱导的软骨分化。总之，本研究证实了E7在BMSCs黏附和活力中的独立作用，并揭示了E7通过H19/miR675轴对BMSCs的促软骨作用。这些结果有助于建立基于利用内源性BMSCs进行软骨组织再生的新治疗策略。
