ArticleProceedings of the National Academy of Sciences of the United States of America2016
Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Understanding Tendons: Lessons from Transgenic Mouse Models.Stem cells and development · 2018Pooled it
- Tendon stem/progenitor cells in heterotopic ossification: functional regulation, molecular mechanisms and targeted therapeutic strategies.Journal of orthopaedic translation · 2026Review
- Targeting coupling of type H-like vessels and cell fate transition to delay soft tissue aging.Nature communications · 2026Article
- Integrin inhibition facilitates fibrocartilaginous transformation in connective tissue in osteoarthritis.Science advances · 2026Article
- The myodural bridge complex: a comprehensive review of morphology, physiology, developmental biology and pathology.Frontiers in medicine · 2026Review
- Impact of mechanotransduction on gene expression changes in periodontal ligament during orthodontic tooth movement.Journal of bone and mineral metabolism · 2025Article
- Tendon mechanobiology in the context of tendon biofabrication.Frontiers in bioengineering and biotechnology · 2025Review
- Molecular basis of individual locomotor function: Integrated understanding of gene expression regulation in the development and homeostasis of the musculoskeletal system.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- Molecular mechanisms of mechanosensing and plasticity of tendons and ligaments.Journal of biochemistry · 2024Review
- The role of mechanotransduction in tendon.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Review
- The Mohawk homeobox gene represents a marker and osteo-inhibitory factor in calvarial suture osteoprogenitor cells.Cell death & disease · 2024Article
- The Transcription Factor Mohawk Facilitates Skeletal Muscle Repair via Modulation of the Inflammatory Environment.International journal of molecular sciences · 2024Article
- Macromolecular crowding in human tenocyte and skin fibroblast cultures: A comparative analysis.Materials today. Bio · 2024Article
- The essential role ofRegenerative therapy · 2024Article
- Article
- Role of hedgehog signaling in the pathogenesis and therapy of heterotopic ossification.Frontiers in cell and developmental biology · 2024Review
- Chronological Changes in the Expression and Localization of Sox9 between Achilles Tendon Injury and Functional Recovery in Mice.International journal of molecular sciences · 2023Article
- Nanofiber matrix formulations for the delivery of Exendin-4 for tendon regeneration:Bioactive materials · 2023Article
- Rats lacking Ucp1 present a novel translational tool for the investigation of thermogenic adaptation during cold challenge.Acta physiologica (Oxford, England) · 2023Article
- Parishin A-loaded mesoporous silica nanoparticles modulate macrophage polarization to attenuate tendinopathy.NPJ Regenerative medicine · 2023Article
17 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
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Cell-based or pharmacological approaches for promoting tendon repair are currently not available because the molecular mechanisms of tendon development and healing are not well understood. Although analysis of knockout mice provides many critical insights, small animals such as mice have some limitations. In particular, precise physiological examination for mechanical load and the ability to obtain a sufficient number of primary tendon cells for molecular biology studies are challenging using mice. Here, we generated Mohawk (Mkx)(-/-) rats by using CRISPR/Cas9, which showed not only systemic hypoplasia of tendons similar to Mkx(-/-) mice, but also earlier heterotopic ossification of the Achilles tendon compared with Mkx(-/-) mice. Analysis of tendon-derived cells (TDCs) revealed that Mkx deficiency accelerated chondrogenic and osteogenic differentiation, whereas Mkx overexpression suppressed chondrogenic, osteogenic, and adipogenic differentiation. Furthermore, mechanical stretch stimulation of Mkx(-/-) TDCs led to chondrogenic differentiation, whereas the same stimulation in Mkx(+/+) TDCs led to formation of tenocytes. ChIP-seq of Mkx overexpressing TDCs revealed significant peaks in tenogenic-related genes, such as collagen type (Col)1a1 and Col3a1, and chondrogenic differentiation-related genes, such as SRY-box (Sox)5, Sox6, and Sox9 Our results demonstrate that Mkx has a dual role, including accelerating tendon differentiation and preventing chondrogenic/osteogenic differentiation. This molecular network of Mkx provides a basis for tendon physiology and tissue engineering.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.