ArticleThe Journal of biological chemistry2010
Oscillatory flow-induced proliferation of osteoblast-like cells is mediated by alphavbeta3 and beta1 integrins through synergistic interactions of focal adhesion kinase and Shc with phosphatidylinositol 3-kinase and the Akt/mTOR/p70S6K pathway.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- Protein kinase G and focal adhesion kinase converge on Src/Akt/β-catenin signaling module in osteoblast mechanotransduction.The Journal of biological chemistry · 2012Trial
- Integrin αVβ3 as a context‑dependent regulator of bone homeostasis: Insights into osteoporosis pathogenesis and therapeutic targeting (Review).Molecular medicine reports · 2026Review
- Cellular mechanometabolism: stimuli and implications.EMBO reports · 2026Review
- Stigmasterol upregulates Akt/mTOR/p70S6K signaling through SYVN1 to alleviate osteoporosis in ovariectomized rats.European journal of nutrition · 2026Article
- Targeting integrin αVβ3-Ptgs2-mTOR signaling rescues bone formation in osteoporosis: from molecular mechanism toward therapy.Cellular & molecular biology letters · 2026Article
- Local abaloparatide administration promotes in situ alveolar bone augmentation via FAK-mediated periosteal osteogenesis.International journal of oral science · 2025Article
- Hemodynamic disturbance and mTORC1 activation: Unveiling the biomechanical pathogenesis of thoracic aortic aneurysms in Marfan syndrome.Journal of pharmaceutical analysis · 2025Article
- Research progress on the regulatory mechanism of integrin-mediated mechanical stress in cells involved in bone metabolism.Journal of cellular and molecular medicine · 2024Review
- Tissue Extract from Brittle Star Undergoing Arm Regeneration Promotes Wound Healing in Rat.Marine drugs · 2023Article
- Roles of focal adhesion proteins in skeleton and diseases.Acta pharmaceutica Sinica. B · 2023Review
- Gabapentin Disrupts Binding of Perlecan to the αBiomolecules · 2022Article
- Cell senescence alters responses of porcine trabecular meshwork cells to shear stress.Frontiers in cell and developmental biology · 2022Article
- Mechanosensitive miR-100 coordinates TGFβ and Wnt signaling in osteocytes during fluid shear stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche.Biophysical journal · 2021Article
- Microfluidic devices for studying coagulation biology.Seminars in cell & developmental biology · 2021Review
- CCN1/Cyr61 Is Required in Osteoblasts for Responsiveness to the Anabolic Activity of PTH.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Biocompatibility Investigation of Hybrid Organometallic Polymers for Sub-Micron 3D Printing via Laser Two-Photon Polymerisation.Materials (Basel, Switzerland) · 2019Article
- Integrins in Osteocyte Biology and Mechanotransduction.Current osteoporosis reports · 2019Review
- Estrogen deficiency impairs integrin αScientific reports · 2019Article
- A Fluidic Culture Platform for Spatially Patterned Cell Growth, Differentiation, and Cocultures.Tissue engineering. Part A · 2018Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Interstitial flow in and around bone tissue is oscillatory in nature and affects the mechanical microenvironment for bone cell growth and formation. We investigated the role of oscillatory shear stress (OSS) in modulating the proliferation of human osteoblast-like MG63 cells and its underlying mechanisms. Application of OSS (0.5 +/- 4 dynes/cm(2)) to MG63 cells induced sustained activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR/p70S6K (p70S6 kinase) signaling cascades and hence cell proliferation, which was accompanied by increased expression of cyclins A and D1, cyclin-dependent protein kinases-2, -4, and -6, and bone formation-related genes (c-fos, Egr-1, and Cox-2) and decreased expression of p21(CIP1) and p27(KIP1). OSS-induced activation of PI3K/Akt/mTOR/p70S6K and cell proliferation were inhibited by specific antibodies or small interference RNAs of alpha(v)beta(3) and beta(1) integrins and by dominant-negative mutants of Shc (Shc-SH2) and focal adhesion kinase (FAK) (FAK(F397Y)). Co-immunoprecipitation assay showed that OSS induces sustained increases in association of Shc and FAK with alpha(v)beta(3) and beta(1) integrins and PI3K subunit p85, which were abolished by transfecting the cells with FAK(F397Y) or Shc-SH2. OSS also induced sustained activation of ERK, which was inhibited by the specific PI3K inhibitor LY294002 and was required for OSS-induced activation of mTOR/p70S6K and proliferation in MG63 cells. Our findings provide insights into the mechanisms by which OSS induces osteoblast-like cell proliferation through activation of alpha(v)beta(3) and beta(1) integrins and synergistic interactions of FAK and Shc with PI3K, leading to the modulation of downstream ERK and Akt/mTOR/p70S6K pathways.
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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.