ArticleStem cells (Dayton, Ohio)2013
Mechanically activated Fyn utilizes mTORC2 to regulate RhoA and adipogenesis in mesenchymal stem cells.
Article in Stem cells (Dayton, Ohio), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Targeting mTOR in Systemic Lupus Erythematosus: From Immune Cell Dysfunction to Clinical Translation.Journal of inflammation research · 2026Review
- Fyn Kinase: A Potential Target in Glucolipid Metabolism and Diabetes Mellitus.Current issues in molecular biology · 2025Review
- Small Accelerations of the cell generate sufficient nuclear motion to modulate transcriptional activity, driving cellular response independent of matrix strain.bioRxiv : the preprint server for biology · 2025Article
- Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.Mechanobiology in medicine · 2024Article
- Dynamic strain and β-catenin mediated suppression of interferon responsive genes in quiescent mesenchymal stromal/stem cells.Biochemistry and biophysics reports · 2024Article
- Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss.Journal of clinical medicine · 2024Article
- Osterix-driven LINC complex disruption in vivo diminishes osteogenesis at 8 weeks but not at 15 weeks.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024Article
- CD3ζ-Mediated Signaling Protects Retinal Ganglion Cells in Glutamate Excitotoxicity of the Retina.Cells · 2024Article
- Loss of the auxiliary αJBMR plus · 2024Article
- Anoctamin-1 is induced by TGF-β and contributes to lung myofibroblast differentiation.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Anoctamin-1 is induced by TGF-beta and contributes to lung myofibroblast differentiation.bioRxiv : the preprint server for biology · 2023Article
- Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells.Cell reports · 2023Article
- Inflammation Responses to Bone Scaffolds under Mechanical Stimuli in Bone Regeneration.Journal of functional biomaterials · 2023Review
- A Simplified and Effective Approach for the Isolation of Small Pluripotent Stem Cells Derived from Human Peripheral Blood.Biomedicines · 2023Article
- Gabapentin Disrupts Binding of Perlecan to the αBiomolecules · 2022Article
- The skeleton in a physical world.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Inhibition of focal adhesion turnover prevents osteoblastic differentiation through β-catenin mediated transduction of pro-osteogenic substrate.Journal of biomedical materials research. Part B, Applied biomaterials · 2022Article
- Mechanically Induced Nuclear Shuttling of β-Catenin Requires Co-transfer of Actin.Stem cells (Dayton, Ohio) · 2022Article
- Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation.Scientific reports · 2021Article
- TM9SF4 is a novel regulator in lineage commitment of bone marrow mesenchymal stem cells to either osteoblasts or adipocytes.Stem cell research & therapy · 2021Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Mechanical strain provides an anti-adipogenic, pro-osteogenic stimulus to mesenchymal stem cells (MSC) through generating intracellular signals and via cytoskeletal restructuring. Recently, mTORC2 has been shown to be a novel mechanical target critical for the anti-adipogenic signal leading to preservation of β-catenin. As mechanical activation of mTORC2 requires focal adhesions (FAs), we asked whether proximal signaling involved Src and FAK, which are early responders to integrin-FA engagement. Application of mechanical strain to marrow-derived MSCs was unable to activate mTORC2 when Src family kinases were inhibited. Fyn, but not Src, was specifically required for mechanical activation of mTORC2 and was recruited to FAs after strain. Activation of mTORC2 was further diminished following FAK inhibition, and as FAK phosphorylation (Tyr-397) required Fyn activity, provided evidence of Fyn/FAK cooperativity. Inhibition of Fyn also prevented mechanical activation of RhoA as well as mechanically induced actin stress fiber formation. We thus asked whether RhoA activation by strain was dependent on mTORC2 downstream of Fyn. Inhibition of mTORC2 or its downstream substrate, Akt, both prevented mechanical RhoA activation, indicating that Fyn/FAK affects cytoskeletal structure via mTORC2. We then sought to ascertain whether this Fyn-initiated signal pathway modulated MSC lineage decisions. siRNA knockdown of Fyn, but not Src, led to rapid attainment of adipogenic phenotype with significant increases in adipocyte protein 2, peroxisome proliferator-activated receptor gamma, adiponectin, and perilipin. As such, Fyn expression in mdMSCs contributes to basal cytoskeletal architecture and, when associated with FAs, functions as a proximal mechanical effector for environmental signals that influence MSC lineage allocation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.