Department of Orthopaedics, Kangnam Sacred Heart Hospital, Hallym University School of Medicine, Seoul, Korea.
Clin Orthop Surg. 2023 Jun;15(3):463-476. doi: 10.4055/cios22237. Epub 2023 May 15.
Degenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expression and regulation of tendon injury and healing, we attempted to evaluate the combinatorial effect of selected miRNAs for better healing of degenerative tendinopathy.
The present study was designed to evaluate the combinatorial effect of two miRNAs (has-miR-140 and has-miR-135) in the healing process of the tendon. Publicly available information/data were retrieved from appropriate platforms such as PubMed. Only molecular data, directly associated with tendinopathies, including genes/proteins and miRNAs, were used in this study. The miRNAs involved in tendinopathy were analyzed by a Bioinformatics tools (e.g., TargetScan, miRDB, and the RNA22v2). Interactive involvement of the miRNAs with key proteins involved in tendinopathy was predicted by the Insilco approach.
Based on information available in the public domain, tendon healing-associated miRNAs were predicted to explore their therapeutic potentials. Based on computation analysis, focusing on the potential regulatory effect on tendon healing, the miR-135 and miR-140 were selected for this study. These miRNAs were found as key players in tendon healing through Rho-associated coiled-coil containing protein kinase 1 (ROCK1), IGF-1/PI3K/Akt, PIN, and Wnt signaling pathways. It was also predicted that these miRNAs may reprogram the cells to induce proliferation and differentiation activity. Many miRNAs are likely to regulate genes important for the tendinopathy healing process, and the result of this study allows an approach for miRNA-mediated regeneration of the tenocyte for tendon healing. Based on computational analysis, the role of these miRNAs in different pathways was established, and the results provided insights into the combinatorial approach of miRNA-mediated cell reprogramming.
In this study, the association between miRNAs and the disease was evaluated to correlate the tendinopathy genes and the relevant role of different miRNAs in their regulation. Through this study, it was established that the synergistic effect of more than one miRNA on directed reprogramming of the cell could be helpful in the regeneration of damaged tissue. It is anticipated that this study will be helpful for the design of miRNA cocktails for the orchestration of cellular reprogramming events.
退行性肌腱病是一种由于高疼痛导致运动受限的疾病，严重影响生产力和生活质量。愈合过程是一个复杂的现象，涉及一系列细胞内和细胞间过程。肌腱细胞的增殖和分化是治疗退行性肌腱病的主要和必要过程。最近，通过特定途径的 microRNA（miRNA）介导的细胞功能重编程为新的再生治疗方法的发展开辟了道路。基于关于肌腱损伤和愈合的基因表达和调控的信息，我们试图评估选定的 miRNAs 的组合效应，以更好地治疗退行性肌腱病。
本研究旨在评估两种 miRNA（has-miR-140 和 has-miR-135）在肌腱愈合过程中的组合效应。从适当的平台（如 PubMed）检索可公开获得的信息/数据。本研究仅使用与肌腱病直接相关的分子数据，包括基因/蛋白质和 miRNAs。通过生物信息学工具（例如 TargetScan、miRDB 和 RNA22v2）分析涉及肌腱病的 miRNAs。通过计算分析预测 miRNAs 与涉及肌腱病的关键蛋白的相互作用。
基于公共领域的可用信息，预测了与肌腱愈合相关的 miRNAs，以探索其治疗潜力。基于计算分析，重点关注对肌腱愈合的潜在调节作用，选择 miR-135 和 miR-140 进行本研究。通过 Rho 相关卷曲螺旋蛋白激酶 1（ROCK1）、IGF-1/PI3K/Akt、PIN 和 Wnt 信号通路，发现这些 miRNAs 是肌腱愈合的关键参与者。还预测这些 miRNAs 可能会重新编程细胞以诱导增殖和分化活性。许多 miRNAs 可能调节与肌腱病愈合过程相关的重要基因，本研究的结果允许采用 miRNA 介导的 tenocyte 再生方法治疗肌腱。基于计算分析，确定了这些 miRNAs 在不同途径中的作用，并为 miRNA 介导的细胞重编程的组合方法提供了见解。
在这项研究中，评估了 miRNAs 与疾病的关联，以将肌腱病基因与不同 miRNAs 在其调节中的相关作用联系起来。通过这项研究，确定了一种以上 miRNA 对定向细胞重编程的协同作用可能有助于受损组织的再生。预计这项研究将有助于设计用于协调细胞重编程事件的 miRNA 鸡尾酒。
