ArticlePloS one2015
Activin Receptor-Like Kinase Receptors ALK5 and ALK1 Are Both Required for TGFβ-Induced Chondrogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- 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
- Dose-Dependent Effects of TGF-β Inhibition on Osteoblast Differentiation and Wound Healing.Current issues in molecular biology · 2025Article
- Sodium Hyaluronate-PDGF Repairs Cartilage and Subchondral Bone Microenvironment via HIF-1α-VEGF-Notch and SDF-1-CXCR4 Inhibition in Osteoarthritis.Journal of cellular and molecular medicine · 2025Article
- Transforming growth factor-β receptor 1: An intervention target for genetic poor cartilage quality induced by prenatal dexamethasone exposure.Journal of advanced research · 2023Article
- Macrophage TGF-β signaling is critical for wound healing with heterotopic ossification after trauma.JCI insight · 2022Article
- Low-Dose-Rate Radiation-Induced Secretion of TGF-β3 Together with an Activator in Small Extracellular Vesicles Modifies Low-Dose Hyper-Radiosensitivity through ALK1 Binding.International journal of molecular sciences · 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
- Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway.International journal of molecular sciences · 2021Article
- Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities.International journal of molecular sciences · 2021Review
- Fluid shear stress generates a unique signaling response by activating multiple TGFβ family type I receptors in osteocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Mesenchymal stem cells: amazing remedies for bone and cartilage defects.Stem cell research & therapy · 2020Review
- Structure-Based Virtual Screening, Molecular Dynamics and Binding Free Energy Calculations of Hit Candidates as ALK-5 Inhibitors.Molecules (Basel, Switzerland) · 2020Article
- Predicting and Promoting Human Bone Marrow MSC Chondrogenesis by Way of TGFβ Receptor Profiles: Toward Personalized Medicine.Frontiers in bioengineering and biotechnology · 2020Article
- Perspectives of small molecule inhibitors of activin receptor‑like kinase in anti‑tumor treatment and stem cell differentiation (Review).Molecular medicine reports · 2019Review
- Co-treatment of TGF-β3 and BMP7 is superior in stimulating chondrocyte redifferentiation in both hypoxia and normoxia compared to single treatments.Scientific reports · 2018Article
- Research Progress on the Role and Mechanism of Action of Activin A in Brain Injury.Frontiers in neuroscience · 2018Review
- Type III Transforming Growth Factor-Stem cells international · 2018Article
- Activin and Nodal Are Not Suitable Alternatives to TGFβ for Chondrogenic Differentiation of Mesenchymal Stem Cells.Cartilage · 2017Article
- The Good the Bad and the Ugly of Glycosaminoglycans in Tissue Engineering Applications.Pharmaceuticals (Basel, Switzerland) · 2017Review
- The changing role of TGFβ in healthy, ageing and osteoarthritic joints.Nature reviews. Rheumatology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionBone marrow-derived mesenchymal stem cells (BMSCs) are promising for cartilage regeneration because BMSCs can differentiate into cartilage tissue-producing chondrocytes. Transforming Growth Factor β (TGFβ) is crucial for inducing chondrogenic differentiation of BMSCs and is known to signal via Activin receptor-Like Kinase (ALK) receptors ALK5 and ALK1. Since the specific role of these two TGFβ receptors in chondrogenesis is unknown, we investigated whether ALK5 and ALK1 are expressed in BMSCs and whether both receptors are required for chondrogenic differentiation of BMSCs. MATERIALS &
methodsALK5 and ALK1 gene expression in human BMSCs was determined with RT-qPCR. To induce chondrogenesis, human BMSCs were pellet-cultured in serum-free chondrogenic medium containing TGFβ1. Chondrogenesis was evaluated by aggrecan and collagen type IIα1 RT-qPCR analysis, and histological stainings of proteoglycans and collagen type II. To overexpress constitutively active (ca) receptors, BMSCs were transduced either with caALK5 or caALK1. Expression of ALK5 and ALK1 was downregulated by transducing BMSCs with shRNA against ALK5 or ALK1.
resultsALK5 and ALK1 were expressed in in vitro-expanded as well as in pellet-cultured BMSCs from five donors, but mRNA levels of both TGFβ receptors did not clearly associate with chondrogenic induction. TGFβ increased ALK5 and decreased ALK1 gene expression in chondrogenically differentiating BMSC pellets. Neither caALK5 nor caALK1 overexpression induced cartilage matrix formation as efficient as that induced by TGFβ. Moreover, short hairpin-mediated downregulation of either ALK5 or ALK1 resulted in a strong inhibition of TGFβ-induced chondrogenesis.
conclusionALK5 as well as ALK1 are required for TGFβ-induced chondrogenic differentiation of BMSCs, and TGFβ not only directly induces chondrogenesis, but also modulates ALK5 and ALK1 receptor signaling in BMSCs. These results imply that optimizing cartilage formation by mesenchymal stem cells will depend on activation of both receptors.
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