Evidence map›Paper›PMID 40254618›Full record

ArticleNature communications2025

PI3K-Akt signalling regulates Scx-lineage tenocytes and Tppp3-lineage paratenon sheath cells in neonatal tendon regeneration.

Atsushi Goto, Shingo Komura, Koki Kato, Rie Maki, Akihiro Hirakawa, Hitomi Aoki, Hiroyuki Tomita, Jumpei Taguchi, Manabu Ozawa, Takahide Matsushima and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Article
  2. PIEZO1 Is a Contextual Mechanosensor and Its Depletion in Scx-Lineage Cells Accelerates Structural and Functional Recovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  3. Article
  4. The cellular basis of fibrotic tendon healing: now in higher definition.American journal of physiology. Cell physiology · 2026
    Review
  5. Molecular Mechanisms of Rotator Cuff Degeneration Identified by Spatial Transcriptomics and Multiplex Immunofluorescence.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026
    Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Atsushi GotoDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Japan.ORCID http://orcid.org/0000-0002-4005-4041
Shingo KomuraDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Japan. komura.shingo.m7@f.gifu-u.ac.jp.ORCID http://orcid.org/0000-0002-7639-7484
Koki KatoDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Rie MakiDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Akihiro HirakawaDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Hitomi AokiDepartment of Stem Cell and Regenerative Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.ORCID http://orcid.org/0000-0003-3357-9971
Hiroyuki TomitaDepartment of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
Jumpei TaguchiCore Laboratory for Developing Advanced Animal Models, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Manabu OzawaCore Laboratory for Developing Advanced Animal Models, Institute of Medical Science, University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0003-3284-7161
Takahide MatsushimaDepartment of Systems BioMedicine, Institute of Science Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-7110-2261
Akio KishidaDepartment of Material-Based Medical Engineering, Laboratory for Biomaterials and Bioengineering, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Tsuyoshi KimuraMaterials-based Medical Engineering Laboratory, Department of Biomedical Engineering, Faculty of Life Science, Toyo University, Tokyo, Japan.
Hiroshi AsaharaDepartment of Systems BioMedicine, Institute of Science Tokyo, Tokyo, Japan.
Yuuki ImaiDivision of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Toon, Ehime, Japan.ORCID http://orcid.org/0000-0002-6119-0034
Yasuhiro YamadaDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Haruhiko AkiyamaDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Japan.

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) 18K09101MEXT | Japan Society for the Promotion of Science (JSPS) 18K16617MEXT | Japan Society for the Promotion of Science (JSPS) 21H03052MEXT | Japan Society for the Promotion of Science (JSPS) 23K21465MEXT | Japan Society for the Promotion of Science (JSPS) JP18K09101MEXT | Japan Society for the Promotion of Science (JSPS) JP18K16617
6 · The paper itself

Abstract

Tendon injuries are frequently occurring disorders; it is clinically important to enhance tendon regeneration and prevent functional impairment post-injury. While tendon injuries in children heal quickly with minimal scarring, those in adults heal slowly and are accompanied by fibrotic scarring. Therefore, investigating the healing mechanisms after tendon injury, and identifying the factors that regulate the inherent regenerative capacity of tendons are promising approaches to promoting tendon regeneration. Here, we identify that the PI3K-Akt signalling pathway is preferentially upregulated in injured neonatal murine Achilles tendons. Inhibition of PI3K-Akt signalling in a neonatal murine Achilles tendon rupture model decreases cell proliferation and migration in both Scx-lineage intrinsic tenocytes and Tppp3-lineage extrinsic paratenon sheath cells. Moreover, the inhibition of PI3K-Akt signalling decreases stemness and promotes mature tenogenic differentiation in both Scx- and Tppp3-lineage cells. Collectively, these results suggest that PI3K-Akt signalling plays a pivotal role in neonatal tendon regeneration.

Indexed as

Achilles TendonPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRegenerationTendon InjuriesTenocytesAnimalsAnimals, NewbornBasic Helix-Loop-Helix ProteinsCell DifferentiationCell LineageCell MovementCell ProliferationHumansMaleMiceBasic Helix-Loop-Helix ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktScx protein, mouse

Identifiers

PMID40254618
PMCPMC12010001

What OpenQuestion holds

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Registered trials

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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.