Trial reportProceedings of the National Academy of Sciences of the United States of America2014
Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.Journal of orthopaedic surgery and research · 2017Pooled it
- Effects of hypoxia on the biological characteristics of urine-derived stem cells.Frontiers in cell and developmental biology · 2026Article
- Recapitulating hypoxic metabolism in cartilaginous organoids via adaptive cell-matrix interactions enhances histone lactylation and cartilage regeneration.Nature communications · 2025Article
- Mesenchymal stem cells for osteoarthritis: Recent advances in related cell therapy.Bioengineering & translational medicine · 2025Review
- Functionalized Annealed Microgels for Spatial Control of Osteogenic and Chondrogenic Differentiation.Advanced functional materials · 2024Article
- 3D printed hybrid scaffolds do not induce adverse inflammation in mice and direct human BM-MSC chondrogenesisBiomaterials and biosystems · 2024Article
- Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells.Biomaterials · 2023Article
- Suppressing Chondrocyte Hypertrophy to Build Better Cartilage.Bioengineering (Basel, Switzerland) · 2023Review
- Physioxic Culture of Chondrogenic Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Hypoxia promotes osteogenesis by facilitating acetyl-CoA-mediated mitochondrial-nuclear communication.The EMBO journal · 2022Article
- Close-to-native bone repair via tissue-engineered endochondral ossification approaches.iScience · 2022Review
- Hypoxia promotes differentiation of pure cartilage from human induced pluripotent stem cells.Molecular medicine reports · 2022Article
- Infrapatellar Fat Pads-Derived Stem Cell Is a Favorable Cell Source for Articular Cartilage Tissue Engineering: AnCartilage · 2021Article
- Self-Oxygenation of Tissues Orchestrates Full-Thickness Vascularization of Living Implants.Advanced functional materials · 2021Article
- Time-dependently Appeared Microenvironmental Changes and Mechanism after Cartilage or Joint Damage and the Influences on Cartilage Regeneration.Organogenesis · 2021Review
- Mesenchymal Stromal Cell Differentiation for Generating Cartilage and Bone-Like Tissues In Vitro.Cells · 2021Article
- Turning Nature's own processes into design strategies for living bone implant biomanufacturing: a decade of Developmental Engineering.Advanced drug delivery reviews · 2021Review
- Differential Production of Cartilage ECM in 3D Agarose Constructs by Equine Articular Cartilage Progenitor Cells and Mesenchymal Stromal Cells.International journal of molecular sciences · 2020Article
- Article
- Adipose-derived stem cells improve tendon repair and prevent ectopic ossification in tendinopathy by inhibiting inflammation and inducing neovascularization in the early stage of tendon healing.Regenerative therapy · 2020Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Actively steering the chondrogenic differentiation of mesenchymal stromal cells (MSCs) into either permanent cartilage or hypertrophic cartilage destined to be replaced by bone has not yet been possible. During limb development, the developing long bone is exposed to a concentration gradient of oxygen, with lower oxygen tension in the region destined to become articular cartilage and higher oxygen tension in transient hypertrophic cartilage. Here, we prove that metabolic programming of MSCs by oxygen tension directs chondrogenesis into either permanent or transient hyaline cartilage. Human MSCs chondrogenically differentiated in vitro under hypoxia (2.5% O2) produced more hyaline cartilage, which expressed typical articular cartilage biomarkers, including established inhibitors of hypertrophic differentiation. In contrast, normoxia (21% O2) prevented the expression of these inhibitors and was associated with increased hypertrophic differentiation. Interestingly, gene network analysis revealed that oxygen tension resulted in metabolic programming of the MSCs directing chondrogenesis into articular- or epiphyseal cartilage-like tissue. This differentiation program resembled the embryological development of these distinct types of hyaline cartilage. Remarkably, the distinct cartilage phenotypes were preserved upon implantation in mice. Hypoxia-preconditioned implants remained cartilaginous, whereas normoxia-preconditioned implants readily underwent calcification, vascular invasion, and subsequent endochondral ossification. In conclusion, metabolic programming of MSCs by oxygen tension provides a simple yet effective mechanism by which to direct the chondrogenic differentiation program into either permanent articular-like cartilage or hypertrophic cartilage that is destined to become endochondral bone.
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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.