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Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy

BACKGROUND: 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 th...

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Autores principales: Morya, Vivek Kumar, Lee, Ho-Won, Park, Chang-Wook, Park, Chang-Won, Hyun, Jin Tak, Noh, Kyu-Cheol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Orthopaedic Association 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232305/
https://www.ncbi.nlm.nih.gov/pubmed/37274502
http://dx.doi.org/10.4055/cios22237
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author Morya, Vivek Kumar
Lee, Ho-Won
Park, Chang-Wook
Park, Chang-Won
Hyun, Jin Tak
Noh, Kyu-Cheol
author_facet Morya, Vivek Kumar
Lee, Ho-Won
Park, Chang-Wook
Park, Chang-Won
Hyun, Jin Tak
Noh, Kyu-Cheol
author_sort Morya, Vivek Kumar
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-102323052023-06-02 Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy Morya, Vivek Kumar Lee, Ho-Won Park, Chang-Wook Park, Chang-Won Hyun, Jin Tak Noh, Kyu-Cheol Clin Orthop Surg Original Article BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. The Korean Orthopaedic Association 2023-06 2023-05-15 /pmc/articles/PMC10232305/ /pubmed/37274502 http://dx.doi.org/10.4055/cios22237 Text en Copyright © 2023 by The Korean Orthopaedic Association https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Morya, Vivek Kumar
Lee, Ho-Won
Park, Chang-Wook
Park, Chang-Won
Hyun, Jin Tak
Noh, Kyu-Cheol
Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy
title Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy
title_full Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy
title_fullStr Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy
title_full_unstemmed Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy
title_short Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy
title_sort computational analysis of mir-140 and mir-135 as potential targets to develop combinatorial therapeutics for degenerative tendinopathy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232305/
https://www.ncbi.nlm.nih.gov/pubmed/37274502
http://dx.doi.org/10.4055/cios22237
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