ArticleScientific reports2024
Differential Smad2/3 linker phosphorylation is a crosstalk mechanism of Rho/ROCK and canonical TGF-β3 signaling in tenogenic differentiation.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Opposing effects of Rho-associated coiled-coil kinase 1 (ROCK1) and ROCK2 in TGF-β-SMAD signaling.Cell communication and signaling : CCS · 2026Article
- MicroRNA-mediated mechanotransduction and chondrocyte differentiation in mesenchymal stem cells.Animal cells and systems · 2026Review
- Photobiomodulation-Driven Tenogenic Differentiation of MSCs in Hydrogel Culture.International journal of molecular sciences · 2025Article
- No simple way to averaging out: Pooled mesenchymal stromal cells do not reflect average donor characteristics.Regenerative therapy · 2025Article
- An Injectable BMP-2-Releasing Porous Hydrogel Regulating the Paracrine Effects of ADSCs Promotes Tendon-to-Bone Healing in Rotator Cuff Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Aligned nanofiber scaffolds combined with cyclic stretch facilitate mesenchymal stem cell differentiation for ligament engineering.World journal of stem cells · 2025Article
- Global research hotspots of stem cell therapy for rotator cuff injuries: A bibliometric and visualized analysis.Journal of orthopaedics · 2025Article
- Review
- Signaling Pathways Driving MSC Osteogenesis: Mechanisms, Regulation, and Translational Applications.International journal of molecular sciences · 2025Review
- Rap1 Guanosine Triphosphate Hydrolase (GTPase) Regulates Shear Stress-Mediated Adhesion of Mesenchymal Stromal Cells.Biology · 2025Article
- Tendon mechanobiology in the context of tendon biofabrication.Frontiers in bioengineering and biotechnology · 2025Review
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7 authors.
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Abstract
The transforming growth factor (TGF)-β3 is a well-known inducer for tenogenic differentiation, signaling via the Smad2/3 pathway. Furthermore, other factors like extracellular matrix or mechanical force can induce tenogenic differentiation and possibly alter the response to TGF-β3 by signaling via the Rho/ROCK pathway. The aim of this study was to investigate the interplay of Rho/ROCK and TGF-β3/Smad signaling in tenogenic differentiation, with the Smad2/3 molecule hypothesized as a possible interface. Cultured as monolayers or on collagen I matrices, mesenchymal stromal cells (MSC) were treated with the ROCK inhibitor Y-27632 (10 µM), TGF-β3 (10 ng/ml) or both combined. Control cells were cultured accordingly, without Y-27632 and/or without TGF-β3. At different time points, MSC were analyzed by real-time RT-PCR, immunofluorescence, and Western blot. Cultivation of MSC on collagen matrices and ROCK inhibition supported tenogenic differentiation and fostered the effect of TGF-β3. The phosphorylation of the linker region of Smad2 was reduced by cultivation on collagen matrices, but not by ROCK inhibition. The latter, however, led to increased phosphorylation of the linker region of Smad3. In conclusion, collagen matrices and the Rho/ROCK signaling pathway influence the TGF-β3/Smad2/3 pathway by regulating different phosphorylation sites of the Smad linker region.
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