ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Mechanical activation of mammalian target of rapamycin pathway is required for cartilage development.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- CK2.1 Activates Chondrogenesis by Regulation of the p38 Mitogen-Activated Protein Kinase Pathway.Kinases and phosphatases · 2026Article
- Genome-Wide Association Study Reveals Growth-Related SNPs and Candidate Genes in Largemouth Bass (International journal of molecular sciences · 2025Article
- Hippo-PKCζ-NFκB signaling axis: A druggable modulator of chondrocyte responses to mechanical stress.iScience · 2024Article
- Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs.Nature communications · 2024Article
- Look who's TORking: mTOR-mediated integration of cell status and external signals during limb development and endochondral bone growth.Frontiers in cell and developmental biology · 2023Review
- Age-related mechanisms in the context of rheumatic disease.Nature reviews. Rheumatology · 2022Review
- Protein tyrosine phosphatases in skeletal development and diseases.Bone research · 2022Review
- Restraint upon Embryonic MetatarsalInternational journal of molecular sciences · 2021Article
- Progress of Signaling Pathways, Stress Pathways and Epigenetics in the Pathogenesis of Skeletal Fluorosis.International journal of molecular sciences · 2021Review
- mTORC1 is a mechanosensor that regulates surfactant function and lung compliance during ventilator-induced lung injury.JCI insight · 2021Article
- Mechanical Overloading Induced-Activation of mTOR Signaling in Tendon Stem/Progenitor Cells Contributes to Tendinopathy Development.Frontiers in cell and developmental biology · 2021Article
- Evidence that miR-146a attenuates aging- and trauma-induced osteoarthritis by inhibiting Notch1, IL-6, and IL-1 mediated catabolism.Aging cell · 2018Article
- Review
- Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva.The Journal of clinical investigation · 2017Article
- Altered paracrine signaling from the injured knee joint impairs postnatal long bone growth.eLife · 2017Article
- Limb proportions show developmental plasticity in response to embryo movement.Scientific reports · 2017Article
- Chondrocyte-Specific Knockout of TSC-1 Leads to Congenital Spinal Deformity in Mice.BioMed research international · 2017Article
- Gene markers of fracture healing in early stage and the regulatory mechanism during the process using microarray analysis.Acta orthopaedica et traumatologica turcica · 2016Article
- mTORC1 regulates PTHrP to coordinate chondrocyte growth, proliferation and differentiation.Nature communications · 2016Article
- Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases.Nature reviews. Rheumatology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Mechanical stress regulates development by modulating cell signaling and gene expression. However, the cytoplasmic components mediating mechanotransduction remain unclear. In this study, elimination of muscle contraction during chicken embryonic development resulted in a reduction in the activity of mammalian target of rapamycin (mTOR) in the cartilaginous growth plate. Inhibition of mTOR activity led to significant inhibition of chondrocyte proliferation, cartilage tissue growth, and expression of chondrogenic genes, including Indian hedgehog (Ihh), a critical mediator of mechanotransduction. Conversely, cyclic loading (1 Hz, 5% matrix deformation) of embryonic chicken growth plate chondrocytes in 3-dimensional (3D) collagen scaffolding induced sustained activation of mTOR. Mechanical activation of mTOR occurred in serum-free medium, indicating that it is independent of growth factor or nutrients. Treatment of chondrocytes with Rapa abolished mechanical activation of cell proliferation and Ihh gene expression. Cyclic loading of chondroprogenitor cells deficient in SH2-containing protein tyrosine phosphatase 2 (Shp2) further enhanced mechanical activation of mTOR, cell proliferation, and chondrogenic gene expression. This result suggests that Shp2 is an antagonist of mechanotransduction through inhibition of mTOR activity. Our data demonstrate that mechanical activation of mTOR is necessary for cell proliferation, chondrogenesis, and cartilage growth during bone development, and that mTOR is an essential mechanotransduction component modulated by Shp2 in the cytoplasm.
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Registered trials
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