ArticleCells2022
Stage-Dependent Activity and Pro-Chondrogenic Function of PI3K/AKT during Cartilage Neogenesis from Mesenchymal Stromal Cells.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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
16 citing papers in PubMed, 17 citations in OpenAlex.
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- Role of external forces in the mechanobiology of stem and differentiated chondrogenic cells embedded in a tissue-engineered construct for cartilage repair.Journal of biomedical science · 2026Review
- Orchestrating the immuno-chondrogenic microenvironment via a bio-inorganic hybrid microsphere system for tendon-to-bone healing.Materials today. Bio · 2026Article
- Dichotomous SMAD2/3 regulation and selective antihypertrophic activity of heparin during in vitro chondrogenesis of mesenchymal stromal cells.Cellular & molecular biology letters · 2026Article
- Low-Intensity Electric Field Stimulation Modulates Proliferation, Stemness, and Chondrogenesis of Tonsil-Derived Mesenchymal Stem Cells.Tissue engineering and regenerative medicine · 2026Article
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- Three-dimensionally-printed biphasic PCL/Regenerative biomaterials · 2026Article
- Neuro-immune-vascular-stem cell crosstalk in bone/cartilage regeneration: mechanisms, technological advances, and clinical perspectives.Frontiers in bioengineering and biotechnology · 2026Review
- 940-nm Photobiomodulation Enhances ADSC-Mediated Tracheal Cartilage Repair through TRPV1-Associated Calcium Signaling and Mitochondrial Redox Remodeling.Research (Washington, D.C.) · 2026Article
- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- Up IGF-I via high-toughness adaptive hydrogels for remodeling growth plate of children.Regenerative biomaterials · 2025Article
- Honeycomb-like biomimetic scaffold by functionalized antibacterial hydrogel and biodegradable porous Mg alloy for osteochondral regeneration.Frontiers in bioengineering and biotechnology · 2024Article
- Induced regeneration of articular cartilage - identification of a dormant regeneration program for a non-regenerative tissue.Development (Cambridge, England) · 2023Article
- In situ self-assembled organoid for osteochondral tissue regeneration with dual functional units.Bioactive materials · 2023Article
- Tetrahedral framework nucleic acids enhance the chondrogenic potential of human umbilical cord mesenchymal stem cells via the PI3K/AKT axis.Regenerative biomaterials · 2023Article
- Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review).Medicine internationalReview
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differentiating mesenchymal stromal cells (MSCs) into articular chondrocytes (ACs) for application in clinical cartilage regeneration requires a profound understanding of signaling pathways regulating stem cell chondrogenesis and hypertrophic degeneration. Classifying endochondral signals into drivers of chondrogenic speed versus hypertrophy, we here focused on insulin/insulin-like growth factor 1 (IGF1)-induced phosphoinositide 3-kinase (PI3K)/AKT signaling. Aware of its proliferative function during early but not late MSC chondrogenesis, we aimed to unravel the late pro-chondrogenic versus pro-hypertrophic PI3K/AKT role. PI3K/AKT activity in human MSC and AC chondrogenic 3D cultures was assessed via Western blot detection of phosphorylated AKT. The effects of PI3K inhibition with LY294002 on chondrogenesis and hypertrophy were assessed via histology, qPCR, the quantification of proteoglycans, and alkaline phosphatase activity. Being repressed by ACs, PI3K/AKT activity transiently rose in differentiating MSCs independent of TGFβ or endogenous BMP/WNT activity and climaxed around day 21. PI3K/AKT inhibition from day 21 on equally reduced chondrocyte and hypertrophy markers. Proving important for TGFβ-induced SMAD2 phosphorylation and SOX9 accumulation, PI3K/AKT activity was here identified as a required stage-dependent driver of chondrogenic speed but not of hypertrophy. Thus, future attempts to improve MSC chondrogenesis will depend on the adequate stimulation and upregulation of PI3K/AKT activity to generate high-quality cartilage from human MSCs.
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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.