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Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response

Musculoskeletal disorders, such as osteoarthritis and intervertebral disc degeneration are causes of morbidity, which concomitantly burdens the health and social care systems worldwide, with massive costs. Link N peptide has recently been described as a novel anabolic stimulator for intervertebral d...

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Autores principales: Tendulkar, Gauri, Ehnert, Sabrina, Sreekumar, Vrinda, Chen, Tao, Kaps, Hans-Peter, Golombek, Sonia, Wendel, Hans-Peter, Nüssler, Andreas K., Avci-Adali, Meltem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479841/
https://www.ncbi.nlm.nih.gov/pubmed/30959917
http://dx.doi.org/10.3390/ijms20071716
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author Tendulkar, Gauri
Ehnert, Sabrina
Sreekumar, Vrinda
Chen, Tao
Kaps, Hans-Peter
Golombek, Sonia
Wendel, Hans-Peter
Nüssler, Andreas K.
Avci-Adali, Meltem
author_facet Tendulkar, Gauri
Ehnert, Sabrina
Sreekumar, Vrinda
Chen, Tao
Kaps, Hans-Peter
Golombek, Sonia
Wendel, Hans-Peter
Nüssler, Andreas K.
Avci-Adali, Meltem
author_sort Tendulkar, Gauri
collection PubMed
description Musculoskeletal disorders, such as osteoarthritis and intervertebral disc degeneration are causes of morbidity, which concomitantly burdens the health and social care systems worldwide, with massive costs. Link N peptide has recently been described as a novel anabolic stimulator for intervertebral disc repair. In this study, we analyzed the influence on anabolic response, by delivering synthetic Link N encoding mRNA into primary human chondrocytes and mesenchymal stromal cells (SCP1 cells). Furthermore, both cell types were seeded on knitted titanium scaffolds, and the influence of Link N peptide mRNA for possible tissue engineering applications was investigated. Synthetic modified Link N mRNA was efficiently delivered into both cell types and cell transfection resulted in an enhanced expression of aggrecan, Sox 9, and type II collagen with a decreased expression of type X collagen. Interestingly, despite increased expression of BMP2 and BMP7, BMP signaling was repressed and TGFβ signaling was boosted by Link N transfection in mesenchymal stromal cells, suggesting possible regulatory mechanisms. Thus, the exogenous delivery of Link N peptide mRNA into cells augmented an anabolic response and thereby increased extracellular matrix synthesis. Considering these findings, we suppose that the cultivation of cells on knitted titanium scaffolds and the exogenous delivery of Link N peptide mRNA into cells could mechanically support the stability of tissue-engineered constructs and improve the synthesis of extracellular matrix by seeded cells. This method can provide a potent strategy for articular cartilage and intervertebral disc regeneration.
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spelling pubmed-64798412019-04-29 Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response Tendulkar, Gauri Ehnert, Sabrina Sreekumar, Vrinda Chen, Tao Kaps, Hans-Peter Golombek, Sonia Wendel, Hans-Peter Nüssler, Andreas K. Avci-Adali, Meltem Int J Mol Sci Article Musculoskeletal disorders, such as osteoarthritis and intervertebral disc degeneration are causes of morbidity, which concomitantly burdens the health and social care systems worldwide, with massive costs. Link N peptide has recently been described as a novel anabolic stimulator for intervertebral disc repair. In this study, we analyzed the influence on anabolic response, by delivering synthetic Link N encoding mRNA into primary human chondrocytes and mesenchymal stromal cells (SCP1 cells). Furthermore, both cell types were seeded on knitted titanium scaffolds, and the influence of Link N peptide mRNA for possible tissue engineering applications was investigated. Synthetic modified Link N mRNA was efficiently delivered into both cell types and cell transfection resulted in an enhanced expression of aggrecan, Sox 9, and type II collagen with a decreased expression of type X collagen. Interestingly, despite increased expression of BMP2 and BMP7, BMP signaling was repressed and TGFβ signaling was boosted by Link N transfection in mesenchymal stromal cells, suggesting possible regulatory mechanisms. Thus, the exogenous delivery of Link N peptide mRNA into cells augmented an anabolic response and thereby increased extracellular matrix synthesis. Considering these findings, we suppose that the cultivation of cells on knitted titanium scaffolds and the exogenous delivery of Link N peptide mRNA into cells could mechanically support the stability of tissue-engineered constructs and improve the synthesis of extracellular matrix by seeded cells. This method can provide a potent strategy for articular cartilage and intervertebral disc regeneration. MDPI 2019-04-06 /pmc/articles/PMC6479841/ /pubmed/30959917 http://dx.doi.org/10.3390/ijms20071716 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tendulkar, Gauri
Ehnert, Sabrina
Sreekumar, Vrinda
Chen, Tao
Kaps, Hans-Peter
Golombek, Sonia
Wendel, Hans-Peter
Nüssler, Andreas K.
Avci-Adali, Meltem
Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response
title Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response
title_full Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response
title_fullStr Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response
title_full_unstemmed Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response
title_short Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response
title_sort exogenous delivery of link n mrna into chondrocytes and mscs—the potential role in increasing anabolic response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479841/
https://www.ncbi.nlm.nih.gov/pubmed/30959917
http://dx.doi.org/10.3390/ijms20071716
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