Stiff matrices enhance myoblast proliferation, reduce differentiation, and alter the response to fluid shear stress in vitro

Autor: Victor J. B. van Santen, Jenneke Klein-Nulend, Astrid D. Bakker, Richard T. Jaspers
Přispěvatelé: Elderly care medicine, Oral Cell Biology, AMS - Tissue Function & Regeneration, Physiology, AMS - Rehabilitation & Development
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell Biochemistry and Biophysics, 80(1), 161-170. Humana Press
van Santen, V J B, Klein-Nulend, J, Bakker, A D & Jaspers, R T 2022, ' Stiff matrices enhance myoblast proliferation, reduce differentiation, and alter the response to fluid shear stress in vitro ', Cell Biochemistry and Biophysics, vol. 80, no. 1, pp. 161-170 . https://doi.org/10.1007/s12013-021-01050-4
ISSN: 1085-9195
DOI: 10.1007/s12013-021-01050-4
Popis: During myofiber regeneration, myoblasts are continuously subjected to shear stress. It is currently not known whether shear stress affects the regenerative capacity of myoblasts when extracellular matrix (ECM) stiffness increases (e.g. upon aging). Therefore, we aimed to assess (1) whether matrix stiffness and pulsating fluid shear stress affect myoblast proliferation and/or expression of differentiation-associated genes in myoblasts, and (2) whether matrix stiffness modulates the mechanoresponse of myoblasts to pulsating fluid shear stress. Myoblasts were seeded on matrigel-coated polyacrylamide gel matrices of varying stiffness, mimicking young (“soft”, 0.5 kPa) and old ECM (“stiff”, 20 kPa), as well as on matrigel-coated glass matrices with very high stiffness (40 ϺPa), and subjected to 1 h pulsating fluid shear stress (3 Pa/s or 4 Pa/s, 1 Hz). We found enhanced proliferation of myoblasts on stiff matrices, but reduced differentiation compared to myoblasts on soft matrices. Pulsating fluid shear stress significantly upregulated gene expression of proliferation-associated genes C-fos and Il-6, as well as expression of cytoskeletal α-actin in myoblasts seeded on glass. In contrast, pulsating fluid shear stress significantly downregulated gene expression of α-actin and Myogenin in myoblasts seeded on soft matrices. In conclusion, these results suggest that age and disease-associated increased ECM stiffness may contribute to declined regenerative capacity of myoblasts, by reducing their capacity to differentiate into new muscular tissue, at least in the absence of mechanical stimulation.
Databáze: OpenAIRE
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