scholarly journals Rho/ROCK Inhibition Promotes TGF-β3-Induced Tenogenic Differentiation in Mesenchymal Stromal Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Michaela Melzer ◽  
Susanna Schubert ◽  
Simon Franz Müller ◽  
Joachim Geyer ◽  
Alina Hagen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Actin Cytoskeleton ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Nuclear Translocation ◽  
Signalling Molecules ◽  
Tenogenic Differentiation ◽  
Extracellular Matrix Components ◽  
Matrix Components ◽  
Rock Inhibition

Mesenchymal stromal cells (MSC) represent a promising therapeutic tool for tendon regeneration. Their tenogenic differentiation is crucial for tissue engineering approaches and may support their beneficial effects after cell transplantation in vivo. The transforming growth factor (TGF)-β, signalling via intracellular Smad molecules, is a potent paracrine mediator of tenogenic induction. Moreover, scaffold topography or tendon matrix components induced tenogenesis via activation of the Rho/ROCK cascade, which, however, is also involved in pathological adaptations in extracellular matrix pathologies. The aim of this study was to investigate the interplay of Rho/ROCK and TGF-β3/Smad signalling in tenogenic differentiation in both human and equine MSC. Primary equine and human MSC isolated from adipose tissue were cultured as monolayers or on tendon-derived decellularized scaffolds to evaluate the influence of the ROCK inhibitor Y-27632 on TGF-β3-induced tenogenic differentiation. The MSC were incubated with and without TGF-β3 (10 ng/ml), Y-27632 (10 μM), or both. On day 1 and day 3, the signalling pathway of TGF-β and the actin cytoskeleton were visualized by Smad 2/3 and phalloidin staining, and gene expression of signalling molecules and tendon markers was assessed. ROCK inhibition was confirmed by disruption of the actin cytoskeleton. Activation of Smad 2/3 with nuclear translocation was evident upon TGF-β3 stimulation. Interestingly, this effect was most pronounced with additional ROCK inhibition in both species ( p < 0.05 in equine MSC). In line with that, the tendon marker scleraxis showed the strongest upregulation when TGF-β3 and ROCK inhibition were combined ( p < 0.05 in human MSC). The regulation pattern of tendon extracellular matrix components and the signalling molecules TGF-β3 and Smad 8 showed differences between human and equine MSC. The obtained results showed that ROCK inhibition promotes the TGF-β3/Smad 2/3 axis, with possible implications for future MSC priming regimes in tendon therapy.

Guided differentiation of bone marrow stromal cells on co-cultured cartilage and bone scaffolds

Soft Matter ◽  
2015 ◽  
Vol 11 (38) ◽  
pp. 7648-7655 ◽  
Author(s):  
Paul Lee ◽  
Katelyn Tran ◽  
Gan Zhou ◽  
Asheesh Bedi ◽  
Namdev B. Shelke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Extracellular Matrix ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Bone Scaffolds ◽  
Extracellular Matrix Components ◽  
Matrix Components ◽  
Osteochondral Tissue ◽  
Tissue Material

A biphasic micro and nanostructured scaffold with hydroxyapatite and extracellular matrix components was created for the regeneration of osteochondral tissue. Material cues of the biphasic scaffold supported differentiation of bone marrow stromal cells in both osteogenic and chondrogenic lineages.

scholarly journals The E8 subfragment of laminin promotes locomotion of myoblasts over extracellular matrix.

1989 ◽  
Vol 109 (2) ◽  
pp. 799-809 ◽  
Author(s):  
S L Goodman ◽  
G Risse ◽  
K von der Mark
Keyword(s):  
Extracellular Matrix ◽  
Actin Cytoskeleton ◽  
Cell Body ◽  
Stress Fibers ◽  
Mixed Substrate ◽  
Main Form ◽  
The Poor ◽  
Extracellular Matrix Components ◽  
Immunofluorescence Studies ◽  
Matrix Components

The locomotion of murine myoblasts over the extracellular matrix components laminin and fibronectin was analyzed using quantitative videomicroscopy, and the organization of the cytoskeleton was observed in parallel immunofluorescence studies. Cells plated on the laminin-nidogen complex locomoted twice as fast as on laminin alone. The main form of translocation on laminin was a jerky cycle of prolonged lamellipod extension followed by rapid (approximately 200- less than 500 microh h-1) movement of the cell body into the extended lamellipod. The locomotion-stimulating activity of laminin resides in the elastase digestion fragment E8, part of the laminin long arm, while the E1-4 fragment containing the three short arms is inactive. Myoblasts moved poorly over fibronectin irrespective of whether high, intermediate, or low coating concentrations were used (approximately 5,000- approximately 10 fmol cm-2). In contrast, the locomotory responses both to laminin and to E8 peaked sharply at coating concentrations approximately 20-50 fmol cm-2 and decreased at higher concentrations. This response corresponds to that expected for a haptotactic stimulant. When cells locomoted over a mixed substrate of laminin and fibronectin, the fibronectin effects appeared to predominate. The cytoskeleton has been implicated in many cellular motile processes. Within 6 h on fibronectin many cells expressed vinculin-containing focal contacts, elaborated stress fibers and had periodically organized alpha actinin, whereas on laminin, most cells showed diffuse vinculin and alpha actinin and a fine meshlike actin cytoskeleton. We conclude that the poor locomotion of cells over fibronectin is because of the cytoskeletal stabilization it induces.

scholarly journals Age related extracellular matrix and interstitial cell phenotype in pulmonary valves

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shaohua Wu ◽  
Vikas Kumar ◽  
Peng Xiao ◽  
Mitchell Kuss ◽  
Jung Yul Lim ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Heart Valve ◽  
Cell Phenotype ◽  
Primary Concern ◽  
Ross Operation ◽  
Age Related ◽  
Cardiovascular Morbidity And Mortality ◽  
Extracellular Matrix Components ◽  
Matrix Components

AbstractHeart valve disease is a common manifestation of cardiovascular disease and is a significant cause of cardiovascular morbidity and mortality worldwide. The pulmonary valve (PV) is of primary concern because of its involvement in common congenital heart defects, and the PV is usually the site for prosthetic replacement following a Ross operation. Although effects of age on valve matrix components and mechanical properties for aortic and mitral valves have been studied, very little is known about the age-related alterations that occur in the PV. In this study, we isolated PV leaflets from porcine hearts in different age groups (~ 4–6 months, denoted as young versus ~ 2 years, denoted as adult) and studied the effects of age on PV leaflet thickness, extracellular matrix components, and mechanical properties. We also conducted proteomics and RNA sequencing to investigate the global changes of PV leaflets and passage zero PV interstitial cells in their protein and gene levels. We found that the size, thickness, elastic modulus, and ultimate stress in both the radial and circumferential directions and the collagen of PV leaflets increased from young to adult age, while the ultimate strain and amount of glycosaminoglycans decreased when age increased. Young and adult PV had both similar and distinct protein and gene expression patterns that are related to their inherent physiological properties. These findings are important for us to better understand the physiological microenvironments of PV leaflet and valve cells for correctively engineering age-specific heart valve tissues.

Production of Extracellular Matrix Components in Tissue-Engineered Blood Vessels

2006 ◽  
Vol 12 (4) ◽  
pp. 831-842 ◽  
Author(s):  
Sepideh Heydarkhan-Hagvall ◽  
Maricris Esguerra ◽  
Gisela Helenius ◽  
Rigmor Söderberg ◽  
Bengt R. Johansson ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Blood Vessels ◽  
Extracellular Matrix Components ◽  
Tissue Engineered Blood Vessels ◽  
Matrix Components

scholarly journals The Role of the Extracellular Matrix Components in Cutaneous Wound Healing

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pawel Olczyk ◽  
Łukasz Mencner ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Wound Repair ◽  
Structural Integrity ◽  
Healing Process ◽  
Cellular Functions ◽  
Extracellular Matrix Components ◽  
Essential Components ◽  
Matrix Components

Wound healing is the physiologic response to tissue trauma proceeding as a complex pathway of biochemical reactions and cellular events, secreted growth factors, and cytokines. Extracellular matrix constituents are essential components of the wound repair phenomenon. Firstly, they create a provisional matrix, providing a structural integrity of matrix during each stage of healing process. Secondly, matrix molecules regulate cellular functions, mediate the cell-cell and cell-matrix interactions, and serve as a reservoir and modulator of cytokines and growth factors’ action. Currently known mechanisms, by which extracellular matrix components modulate each stage of the process of soft tissue remodeling after injury, have been discussed.

Alterations in extracellular matrix components in transplant glomerulopathy

2000 ◽  
Vol 437 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Hyeon Joo Jeong ◽  
Sun Hee Sung ◽  
Soon Won Hong ◽  
Jang Il Moon ◽  
Soon Il Kim ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Matrix Components ◽  
Matrix Components ◽  
Transplant Glomerulopathy
Sign in / Sign up

Export Citation Format

Share Document