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

International Journal of Molecular Sciences

Meltem Avci-Adali¹  Sonia Golombek¹  Hans-Peter Wendel¹  Gauri Tendulkar²  Vrinda Sreekumar²  Tao Chen²  Hans-Peter Kaps²  AndreasK. Nüssler²  Sabrina Ehnert² 

[1] Department of Thoracic and Cardiovascular Surgery, University Hospital Tübingen, Calwerstraße 7/1, 72076 Tübingen, Germany;Siegfried Weller Institute for Trauma Research at the BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstraße 95, 72076 Tübingen, Germany;

关键词: Synthetic mRNA;    Link N peptide;    mRNA delivery;    musculoskeletal disorders;   

DOI  :  10.3390/ijms20071716

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown