ArticleProceedings of the National Academy of Sciences of the United States of America2018
Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 78 citations in OpenAlex.
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- Modular de- and re-construction of vascularized osteochondral tissues in an Organ-on-Chip dual-compartment platform.Journal of orthopaedic translation · 2026Article
- An Organ-on-Chip Platform for Strain-Controlled, Tissue-Specific Compression of Cartilage and Mineralized Osteochondral Interface to Study Mechanical Overloading in Osteoarthritis.Advanced healthcare materials · 2025Article
- Large-scale multicenter study reveals anticitrullinated SR-A peptide antibody as a biomarker and exacerbator for rheumatoid arthritis.Science advances · 2025Article
- Time- and cell-specific activation of BMP signaling restrains chondrocyte hypertrophy.iScience · 2024Article
- Mesenchymal stromal cell chondrogenesis under ALK1/2/3-specific BMP inhibition: a revision of the prohypertrophic signalling network concept.Stem cell research & therapy · 2024Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Review
- Human Mesenchymal Stem Cell-Derived Miniature Joint System for Disease Modeling and Drug Testing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Acellular cartilage matrix biomimetic scaffold with immediate enrichment of autologous bone marrow mononuclear cells to repair articular cartilage defects.Materials today. Bio · 2022Article
- Highly Porous Type II Collagen-Containing Scaffolds for Enhanced Cartilage Repair with Reduced Hypertrophic Cartilage Formation.Bioengineering (Basel, Switzerland) · 2022Article
- Inhibition of BMP signaling with LDN 193189 can influence bone marrow stromal cell fate but does not prevent hypertrophy during chondrogenesis.Stem cell reports · 2022Article
- Research progress of cartilage lubrication and biomimetic cartilage lubrication materials.Frontiers in bioengineering and biotechnology · 2022Review
- Effects of chondrogenic priming duration on mechanoregulation of engineered cartilage.Journal of biomechanics · 2021Article
- Formation of Osteochondral Organoids from Murine Induced Pluripotent Stem Cells.Tissue engineering. Part A · 2021Article
- Characterisation of ovine bone marrow-derived stromal cells (oBMSC) and evaluation of chondrogenically induced micro-pellets for cartilage tissue repair in vivo.Stem cell research & therapy · 2021Article
- A single day of TGF-β1 exposure activates chondrogenic and hypertrophic differentiation pathways in bone marrow-derived stromal cells.Communications biology · 2021Article
- Article
- Engineering Musculoskeletal Grafts for Multi-Tissue Unit Repair: Lessons From Developmental Biology and Wound Healing.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood. Here we tested whether forcing specific early events of articular cartilage development can program hMSC fate toward stable chondrogenesis. Inspired by recent findings that spatial restriction of bone morphogenetic protein (BMP) signaling guides embryonic progenitors toward articular cartilage formation, we hypothesized that selective inhibition of BMP drives the phenotypic stability of hMSC-derived chondrocytes. Two BMP type I receptor-biased kinase inhibitors were screened in a microfluidic platform for their time- and dose-dependent effect on hMSC chondrogenesis. The different receptor selectivity profile of tested compounds allowed demonstration that transient blockade of both ALK2 and ALK3 receptors, while permissive to hMSC cartilage formation, is necessary and sufficient to maintain a stable chondrocyte phenotype. Remarkably, even upon compound removal, hMSCs were no longer competent to undergo hypertrophy in vitro and endochondral ossification in vivo, indicating the onset of a constitutive change. Our findings demonstrate that adult hMSCs effectively share properties of embryonic mesenchyme in the formation of transient but also of stable cartilage. This opens potential pharmacological strategies to articular cartilage regeneration and more broadly indicates the relevance of developmentally inspired protocols to control the fate of adult progenitor cell systems.
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