ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2014
mTORC2 regulates mechanically induced cytoskeletal reorganization and lineage selection in marrow-derived mesenchymal stem cells.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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99 citing papers in PubMed, 152 citations in OpenAlex.
- Mechanometabolism instructs hematopoietic stem cell specification.The Journal of experimental medicine · 2026Article
- mTOR signaling governs the formation of epithelial apical projections via S6K1-RhoA and aPKC-Lgl2 axes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Generation of mature epicardium derived from human-induced pluripotent stem cells via inhibition of mTOR signaling.Nature communications · 2025Article
- The multifaceted anticancer potential of luteolin: involvement of NF-κB, AMPK/mTOR, PI3K/Akt, MAPK, and Wnt/β-catenin pathways.Inflammopharmacology · 2025Review
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- 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
- Nuclear actin structure regulates chromatin accessibility.Nature communications · 2024Article
- Molecular mechanisms of cellular metabolic homeostasis in stem cells.International journal of oral science · 2023Review
- The Spectrum of Molecular Pathways in Gliomas-An Up-to-Date Review.Biomedicines · 2023Review
- Understanding the interplay of membrane trafficking, cell surface mechanics, and stem cell differentiation.Seminars in cell & developmental biology · 2023Review
- Suffruticosol A elevates osteoblast differentiation targeting BMP2-Smad/1/5/8-RUNX2 in pre-osteoblasts.BioFactors (Oxford, England) · 2023Article
- The release of osteoclast-stimulating factors on supraphysiological loading by osteoprogenitors coincides with expression of genes associated with inflammation and cytoskeletal arrangement.Scientific reports · 2022Article
- Gabapentin Disrupts Binding of Perlecan to the αBiomolecules · 2022Article
- Atomic Force Microscopy Cantilever-Based Nanoindentation: Mechanical Property Measurements at the Nanoscale in Air and Fluid.Journal of visualized experiments : JoVE · 2022Article
- Architectural control of mesenchymal stem cell phenotype through nuclear actin.Nucleus (Austin, Tex.) · 2022Article
- The skeleton in a physical world.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- The bone-muscle connection in breast cancer: implications and therapeutic strategies to preserve musculoskeletal health.Breast cancer research : BCR · 2022Review
- Contrasting effects ofeLife · 2022Article
- Long-term osteogenic differentiation of human bone marrow stromal cells in simulated microgravity: novel proteins sighted.Cellular and molecular life sciences : CMLS · 2022Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
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Abstract
The cell cytoskeleton interprets and responds to physical cues from the microenvironment. Applying mechanical force to mesenchymal stem cells induces formation of a stiffer cytoskeleton, which biases against adipogenic differentiation and toward osteoblastogenesis. mTORC2, the mTOR complex defined by its binding partner rictor, is implicated in resting cytoskeletal architecture and is activated by mechanical force. We asked if mTORC2 played a role in mechanical adaptation of the cytoskeleton. We found that during bi-axial strain-induced cytoskeletal restructuring, mTORC2 and Akt colocalize with newly assembled focal adhesions (FA). Disrupting the function of mTORC2, or that of its downstream substrate Akt, prevented mechanically induced F-actin stress fiber development. mTORC2 becomes associated with vinculin during strain, and knockdown of vinculin prevents mTORC2 activation. In contrast, mTORC2 is not recruited to the FA complex during its activation by insulin, nor does insulin alter cytoskeletal structure. Further, when rictor was knocked down, the ability of mesenchymal stem cells (MSC) to enter the osteoblastic lineage was reduced, and when cultured in adipogenic medium, rictor-deficient MSC showed accelerated adipogenesis. This indicated that cytoskeletal remodeling promotes osteogenesis over adipogenesis. In sum, our data show that mTORC2 is involved in stem cell responses to biophysical stimuli, regulating both signaling and cytoskeletal reorganization. As such, mechanical activation of mTORC2 signaling participates in mesenchymal stem cell lineage selection, preventing adipogenesis by preserving β-catenin and stimulating osteogenesis by generating a stiffer cytoskeleton.
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