ArticleConnective tissue research2018
Optimizing a 3D model system for molecular manipulation of tenogenesis.
Article in Connective tissue research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- A systematic investigation of the effects of TGF-β3 and mechanical stimulation on tenogenic differentiation of mesenchymal stromal cells in a poly(ethylene glycol)/gelatin-based hydrogel.Journal of orthopaedic translation · 2023Article
- Three-Dimensional Cell Culture System for Tendon Tissue Engineering.Tissue engineering and regenerative medicine · 2023Review
- Growth factors in the treatment of Achilles tendon injury.Frontiers in bioengineering and biotechnology · 2023Review
- Axin2-lineage cells contribute to neonatal tendon regeneration.Connective tissue research · 2022Article
- Optimizing Tenogenic Differentiation of Equine Adipose-Derived Mesenchymal Stem Cells (eq-ASC) Using TGFB3 Along with BMP Antagonists.Cell journal · 2022Article
- Regulators of collagen crosslinking in developing and adult tendons.European cells & materials · 2022Review
- Transcriptional profiling of mESC-derived tendon and fibrocartilage cell fate switch.Nature communications · 2021Article
- Akt signaling is activated by TGFβ2 and impacts tenogenic induction of mesenchymal stem cells.Stem cell research & therapy · 2021Article
- Tgfβ signaling is required for tenocyte recruitment and functional neonatal tendon regeneration.eLife · 2020Article
- Cell-cell junctions in developing and adult tendons.Tissue barriers · 2020Article
- Tendon stem progenitor cells: Understanding the biology to inform therapeutic strategies for tendon repair.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2019Review
- Models of tendon development and injury.BMC biomedical engineering · 2019Article
- Knockout of hyaluronan synthase 1, but not 3, impairs formation of the retrocalcaneal bursa.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTendon injuries are clinically challenging due to poor healing. A better understanding of the molecular events that regulate tendon differentiation would improve current strategies for repair. The mouse model system has been instrumental to tendon studies and several key molecules were initially established in mouse. However, the study of gene function has been limited by the absence of a standard in vitro tendon system for efficiently testing multiple mutations, physical manipulations, and mis-expression. The purpose of this study is therefore to establish such a system.
methodsWe adapted an existing design for generating three-dimensional (3D) tendon constructs for use with mouse progenitor cells harboring the ScxGFP tendon reporter and the Rosa26-TdTomato Cre reporter. Using these cells, we optimized the parameters for construct formation, inducing tenogenesis via transforming growth factor-β2 (TGFβ2), and genetic recombination via an adenovirus encoding Cre recombinase. Finally, for proof of concept, we used Smad4 floxed cells and tested the robustness of the system for gene knockdown.
resultsWe found that TGFβ2 treatment induced a tenogenic phenotype depending on the timing of initiation. Addition of TGFβ2 after 3D "tensioning" enhanced tendon differentiation. Interestingly, while TGFβ2-induced proliferation depended on Smad4, tenogenic parameters such as ScxGFP expression and fibril diameter were independent of Smad4.
conclusionsOur results demonstrate the feasibility of this optimized system for harnessing the power of mouse genetics for in vitro applications.
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Registered trials
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