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PreprintCited by 19Tendon Structure and TreatmentWound Healing and TreatmentsPeriodontal Regeneration and Treatments

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eEF2 improves dense connective tissue repair and healing outcome by regulating cellular death, autophagy, apoptosis, proliferation and migration

Open access
Chen, Junyu, Wang, Jin, Wu, Xinjie, Simon, Nils, Svensson, Camilla I, Yuan, Juan, Hart, David A, Ahmed, Aisha S, Ackermann, Paul W·2023·Cellular and Molecular Life Sciences
DOI 10.21203/rs.3.rs-2424611/v1PMC PMC10121543

Preprint — published as 10.1007/s00018-023-04776-x

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Abstract

Outcomes following human dense connective tissue (DCT) repair are often variable and suboptimal, resulting in compromised function and development of chronic painful degenerative diseases. Moreover, biomarkers and mechanisms that guide good clinical outcomes after DCT injuries are mostly unknown. Here, we characterize the proteomic landscape of DCT repair following human tendon rupture and its association with long-term patient-reported outcome. Moreover, the regulatory mechanisms of relevant biomarkers were assessed partly by gene silencing experiments. A Mass-Spectrometry based proteomic approach quantified a large number (769) of proteins, including 51 differentially expressed proteins among 20 good versus 20 poor outcome patients. A novel biomarker, elongation factor-2 (eEF2) was identified as being strongly prognostic of the 1-year clinical outcome. Further bioinformatic and experimental investigation revealed that eEF2 positively regulated autophagy, cell proliferation and migration, as well as reduced cell death and apoptosis, leading to improved DCT repair and outcomes. Findings of eEF2 as novel prognostic biomarker could pave the way for new targeted treatments to improve healing outcomes after DCT injuries.

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Metadata

Authors
Chen, J., Wang, J., Wu, X., Simon, N., Svensson, C. I., Yuan, J., Hart, D. A., Ahmed, A. S., & Ackermann, P. W.
Affiliations
  • Karolinska Institutet (SE)
  • Zhejiang Provincial People's Hospital (CN)
  • Peking University (CN)
  • University of Calgary (CA)
  • University of Helsinki (FI)
Corresponding author
  • Chen, Junyu
  • Ahmed, Aisha S
ORCID
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2023-01-11
Volume
80
Issue
5
Pages
128-128
ISSN
1420-682X (ISSN-L)
DOI
10.21203/rs.3.rs-2424611/v1
PMC
PMC10121543
OpenAlex
W4366603743
Cited by
19
References
1
Citations by year
2026: 3 · 2025: 8 · 2024: 5 · 2023: 3
FWCI
5.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Life Sciences (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • European Commission (814244, HORIZON2020)
  • Karolinska Institutet
  • Knut och Alice Wallenbergs Stiftelse (2018.0161, 2019.0437)
  • Vetenskapsrådet (2017-00202, 2018-)
  • Centrum för idrottsforskning (2020-0019, 2022-0066)
  • Stiftelsen Konung Gustaf V:s 80-årsfond (FAI-2019-0611, FAI-2018-0524)
  • Reumatikerförbundet (R‐940565, R-968148)
  • Health and Medical Care Committee of the Regional Executive Board, Region Västra Götaland (SLL20180348)
  • H2020 Marie Skłodowska-Curie Actions (814244)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
  • Health Sciences › Medicine › Surgery › Wound Healing and Treatments
  • Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
Keywords
elongation factor 2, Achilles tendon rupture, tissue repair, prognostic factors, proteomics, autophagy, apoptosis, cell proliferation, cell migration, patient-reported outcomes
MeSH terms
Achilles Tendon, Autophagy, Connective Tissue, Humans, Biomarkers, Cell Death, Apoptosis, Peptide Elongation Factor 2, Proteomics

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