ArticleStem cells and development2012
Bone morphogenetic protein-2-induced signaling and osteogenesis is regulated by cell shape, RhoA/ROCK, and cytoskeletal tension.
Article in Stem cells and development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 234 citations in OpenAlex.
- Bone Morphogenetic Protein-2 Induces Donor-Dependent Osteogenic and Adipogenic Differentiation in Human Adipose Stem Cells.Stem cells translational medicine · 2015Trial
- Synergistic effects of erythropoietin and selenium enhance bone regeneration in ovariectomized rats.Journal of materials science. Materials in medicine · 2026Article
- Leveraging Viscosity to Unlock the Osteogenic Potential of BMP-2 Mimetic DWIVA.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Magnesium-containing implants enhance bone healing: A mechanobiological perspective.Mechanobiology in medicine · 2025Review
- Osteogenesis enhancement by immobilized DOPA-BMP-2 in combination with ultrasonic stimulation.RSC advances · 2025Article
- The guanine nucleotide exchange factor DOCK5 negatively regulates osteoblast differentiation and BMP2-induced bone regeneration via the MKK3/6 and p38 signaling pathways.Experimental & molecular medicine · 2025Article
- Bone-derived nanoparticles (BNPs) enhance osteogenic differentiationNanoscale advances · 2025Article
- Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling.Communications biology · 2025Article
- Involvement of long non-coding RNA (lncRNA) MALAT1 in shear stress regulated adipocyte differentiation.Frontiers in bioengineering and biotechnology · 2025Article
- Tauroursodeoxycholic acid combined with selenium accelerates bone regeneration in ovariectomized rats.Journal of materials science. Materials in medicine · 2024Article
- TGF-β1 promotes osteogenesis of mesenchymal stem cells via integrin mediated mechanical positive autoregulation.iScience · 2024Article
- Mussel-inspired immunomodulatory and osteoinductive dual-functional hydroxyapatite nanoplatform for promoting bone regeneration.Journal of nanobiotechnology · 2024Article
- Cellular and Molecular Mechanisms of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva.Biomedicines · 2024Review
- Recent Developments in Layer-by-Layer Assembly for Drug Delivery and Tissue Engineering Applications.Advanced healthcare materials · 2024Review
- Shear Stress and Sub-Femtomolar Levels of Ligand Synergize to Activate ALK1 Signaling in Endothelial Cells.Cells · 2024Article
- Self-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration.Nature communications · 2023Article
- Preparation and characterization of 3D hydroxyapatite/collagen scaffolds and its application in bone regeneration with bone morphogenetic protein-2.RSC advances · 2023Article
- The regulation and functions of the matricellular CCN proteins induced by shear stress.Journal of cell communication and signaling · 2023Review
- Activin A Limits VEGF-Induced Permeability via VE-PTP.International journal of molecular sciences · 2023Article
- Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Osteogenic differentiation of human mesenchymal stem cells (hMSCs) is classically thought to be mediated by different cytokines such as the bone morphogenetic proteins (BMPs). Here, we report that cell adhesion to extracellular matrix (ECM), and its effects on cell shape and cytoskeletal mechanics, regulates BMP-induced signaling and osteogenic differentiation of hMSCs. Using micropatterned substrates to progressively restrict cell spreading and flattening against ECM, we demonstrated that BMP-induced osteogenesis is progressively antagonized with decreased cell spreading. BMP triggered rapid and sustained RhoA/Rho-associated protein kinase (ROCK) activity and contractile tension only in spread cells, and this signaling was required for BMP-induced osteogenesis. Exploring the molecular basis for this effect, we found that restricting cell spreading, reducing ROCK signaling, or inhibiting cytoskeletal tension prevented BMP-induced SMA/mothers against decapentaplegic (SMAD)1 c-terminal phosphorylation, SMAD1 dimerization with SMAD4, and SMAD1 translocation into the nucleus. Together, these findings demonstrate the direct involvement of cell spreading and RhoA/ROCK-mediated cytoskeletal tension generation in BMP-induced signaling and early stages of in vitro osteogenesis, and highlight the essential interplay between biochemical and mechanical cues in stem cell differentiation.
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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.