Background Perturbation in cell adhesion and growth factor signalling in satellite cells results in decreased muscle regenerative capacity. Cdon (also called Cdo) is a component of cell adhesion complexes implicated in myogenic differentiation, but its role in muscle regeneration remains to be determined. Methods We generated inducible satellite cell‐specific Cdon ablation in mice by utilizing a conditional Cdon allele and Pax7 CreERT2 . To induce Cdon ablation, mice were intraperitoneally injected with tamoxifen (tmx). Using cardiotoxin‐induced muscle injury, the effect of Cdon depletion on satellite cell function was examined by histochemistry, immunostaining, and 5‐ethynyl‐2'‐deoxyuridine (EdU) incorporation assay. Isolated myofibers or myoblasts were utilized to determine stem cell function and senescence. To determine pathways related to Cdon deletion, injured muscles were subjected to RNA sequencing analysis. Results Satellite cell‐specific Cdon ablation causes impaired muscle regeneration with fibrosis, likely attributable to decreased proliferation, and senescence, of satellite cells. Cultured Cdon‐depleted myofibers exhibited 32 ± 9.6% of EdU‐positive satellite cells compared with 58 ± 4.4% satellite cells in control myofibers ( P < 0.05). About 32.5 ± 3.7% Cdon‐ablated myoblasts were positive for senescence‐associated β‐galactosidase (SA‐β‐gal) while only 3.6 ± 0.5% of control satellite cells were positive ( P < 0.001). Transcriptome analysis of muscles at post‐injury Day 4 revealed alterations in genes related to mitogen‐activated protein kinase signalling ( P < 8.29 e −5 ) and extracellular matrix ( P < 2.65 e −24 ). Consistent with this, Cdon‐depleted tibialis anterior muscles had reduced phosphorylated extracellular signal‐regulated kinase (p‐ERK) protein levels and expression of ERK targets, such as Fos (0.23‐fold) and Egr1 (0.31‐fold), relative to mock‐treated control muscles ( P < 0.001). Cdon‐depleted myoblasts exhibited impaired ERK activation in response to basic fibroblast growth factor. Cdon ablation resulted in decreased and/or mislocalized integrin β1 activation in satellite cells (weak or mislocalized integrin1 in tmx = 38.7 ± 1.9%, mock = 21.5 ± 6%, P < 0.05), previously linked with reduced fibroblast growth factor (FGF) responsiveness in aged satellite cells. In mechanistic studies, Cdon interacted with and regulated cell surface localization of FGFR1 and FGFR4, likely contributing to FGF responsiveness of satellite cells. Satellite cells from a progeria model, Zmpste24 −/− myofibers, sho...
Muscle regeneration is a coordinated process that involves proliferation and differentiation of muscle progenitor cells. Activation of MyoD is a key event in myogenic differentiation, which is regulated by p38 mitogen-activated protein kinases (MAPK). In a screen of natural compounds for the enhancement of MyoD activity, dehydrocorydaline (DHC) from the Corydalis tuber was identified. Treatment of C2C12 myoblasts with DHC increased the expression levels of muscle-specific proteins, including MyoD, myogenin and myosin heavy chain. In addition, C2C12 myoblasts exhibited enhanced multinucleated myotube formation without any cytotoxicity. Treatment with DHC elevated p38 MAPK activation and the interaction of MyoD with an E protein, which is likely to result in activation of MyoD and promotion of myoblast differentiation. Furthermore, defects in differentiation-induced p38 MAPK activation and myoblast differentiation induced by depletion of the promyogenic receptor protein Cdo in C2C12 myoblasts were restored by DHC treatment. In conclusion, these results indicated that DHC stimulates p38 MAPK activation, which can enhance heterodimerization of MyoD and E proteins, thus resulting in MyoD activation and myoblast differentiation. These findings suggested that DHC may be considered a potential therapeutic compound for the improvement of muscle stem cell regenerative capacity in injured muscle.
Alumina–glass composites that contain oxidized aluminum were investigated to make shrinkage‐free, all‐ceramic dental porcelain. This was achieved by control of the volume expansion and shrinkage that occur during the aluminum oxidation and densification processes. The dimensional change and strength of the alumina‐glass composites were dependent on the aluminum content and particle size. A shrinkage‐free sample with a strength of 330 MPa and transmittance of 1.21 was fabricated by using 4‐5 vol% of aluminum powder with an average particle size of 6 μ m in the alumina‐glass composite made by the In‐Ceram method.
Herein, an antireflection and superhydrophobic film was obtained by uniformly forming nanostructures on the surface of polyethylene terephthalate (PET) substrate using oxygen plasma without a pattern mask and coating plasma-polymer-fluorocarbon (PPFC) on the nanostructured surface by mid-range frequency sputtering. PPFC/nanostructured-PET showed a reflectance of 4.2%, which is 56% lower than that of the PET film. Haze was also improved. Nanostructured-PET exhibited a superhydrophilic surface due to plasma deformation and a superhydrophobic surface could be realized by coating PPFC on the nanostructured surface. The PPFC coating prevented the aging of polymer film nanostructures and showed excellent durability in a high-temperature and high-humidity environment. It exhibited excellent flexibility to maintain the superhydrophobic surface, even at a mechanical bending radius of 1 mm, and could retain its properties even after repeated bending for 10,000 times.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.