ArticlePloS one2017
Substrate Stiffness Controls Osteoblastic and Chondrocytic Differentiation of Mesenchymal Stem Cells without Exogenous Stimuli.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 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
102 citing papers in PubMed, 217 citations in OpenAlex.
- Engineering Biomimetic 3D Microenvironments for Extracellular Vesicle Programming Toward Clinical Translation.International journal of molecular sciences · 2026Review
- Mechanical Signaling From ECMs to Nuclear Envelopes in Cell Transitions and Fate Decisions: A Review and Perspective on Adhesion-Niche-Based Anti-EndMT and Anti-EMT.Annals of biomedical engineering · 2026Review
- From fitness to fate: Hippo-YAP-mediated cell competition influence on stem cells activity.Bioscience reports · 2026Review
- Natural-Based Nanocomposite Ink Engineering for Seamless Multi-Material Integration in Extrusion-Based 3D Printing.Advanced healthcare materials · 2026Article
- Hurdles to overcome for mesenchymal stem cell translation from bench to bedside.World journal of stem cells · 2025Review
- Nuclear destabilisation - a possible genesis of cancer?Biological reviews of the Cambridge Philosophical Society · 2025Review
- Regulation of the mechanoresponsive Neat1 and PSPC1 by substrate stiffness in TGF-β1-induced renal progenitor cell fate.Journal of biomedical science · 2025Article
- Integrin signaling pathways in mesenchymal stem cells.Stem cell research & therapy · 2025Review
- Self-propagating wave drives morphogenesis of skull bones in vivo.Nature communications · 2025Article
- Mesenchymal stem cell extracellular vesicle vascularization bioactivity and production yield are responsive to cell culture substrate stiffness.Bioengineering & translational medicine · 2025Article
- Article
- Osteoblastic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells on P3HT Thin Polymer Film.Journal of functional biomaterials · 2025Article
- Stem cell-based strategies for intervertebral disc regeneration in degenerative microenvironments: challenges and solutions.Frontiers in cell and developmental biology · 2025Review
- Mechanical and Physical Characterization of a Biphasic 3D Printed Silk-Infilled Scaffold for Osteochondral Tissue Engineering.ACS biomaterials science & engineering · 2024Article
- Reliable Fabrication of Mineral-Graded Scaffolds by Spin-Coating and Laser Machining for Use in Tendon-to-Bone Insertion Repair.Advanced healthcare materials · 2024Article
- Sensing the squeeze: nuclear mechanotransduction in health and disease.Nucleus (Austin, Tex.) · 2024Review
- Article
- The Myofibroblast Fate of Therapeutic Mesenchymal Stromal Cells: Regeneration, Repair, or Despair?International journal of molecular sciences · 2024Review
- Osteoporosis GWAS-implicatedJBMR plus · 2024Article
- β1-Integrin-Mediated Uptake of Chondrocyte Extracellular Vesicles Regulates Chondrocyte Homeostasis.International journal of molecular sciences · 2024Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA) polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffness <10 MPa. Like chondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, β1, and β3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1) in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin β1 plays a pivotal role in this process.
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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.