Evidence map›Paper›PMID 34769331›Full record

ArticleInternational journal of molecular sciences2021

Increased Collagen Crosslinking in Stiff Clubfoot Tissue: Implications for the Improvement of Therapeutic Strategies.

Jarmila Knitlova, Martina Doubkova, Adam Eckhardt, Martin Ostadal, Jana Musilkova, Lucie Bacakova, Tomas Novotny

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
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

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Therapy-Induced ECM Remodeling Creates a Transient Immune Barrier in Residual Melanoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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  7. Recombinant lysyl oxidase effects on embryonic tendon cell phenotype and behavior.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023
    Article
  8. Article
  9. Article
  10. Tendon mechanical properties are enhancedFrontiers in bioengineering and biotechnology · 2022
    Article
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

7 authors at 2 institutions in 1 country.

Jarmila KnitlovaInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
Martina DoubkovaInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.ORCID 0000-0002-4955-4093
Adam EckhardtInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
Martin OstadalDepartment of Orthopaedics, First Faculty of Medicine, Charles University and Na Bulovce Hospital, Budinova 2, 180 81 Prague, Czech Republic.
Jana MusilkovaInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
Lucie BacakovaInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.ORCID 0000-0002-1818-9484
Tomas NovotnyDepartment of Orthopaedics, University J.E. Purkinje and Masaryk Hospital, 401 13 Usti nad Labem, Czech Republic.ORCID 0000-0002-3855-0038
Czech Academy of Sciences · CZCharles University · CZ

Funding

Charles University GA UK No. 410121Krajska zdravotni a.s., Usti nad Labem, Czech Republic No. IGA-KZ-217116003the Ministry of Health of the Czech Republic AZV No. 17-31564A
6 · The paper itself

Abstract

Congenital clubfoot is a complex musculoskeletal deformity, in which a stiff, contracted tissue forms in the medial part of the foot. Fibrotic changes are associated with increased collagen deposition and lysyl oxidase (LOX)-mediated crosslinking, which impair collagen degradation and increase the tissue stiffness. First, we studied collagen deposition, as well as the expression of collagen and the amount of pyridinoline and deoxypyridinoline crosslinks in the tissue of relapsed clubfoot by immunohistochemistry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA). We then isolated fibroblast-like cells from the contracted tissue to study the potential inhibition of these processes in vitro. We assessed the effects of a LOX inhibitor, β-aminopropionitrile (BAPN), on the cells by a hydroxyproline assay, ELISA, and Second Harmonic Generation imaging. We also evaluated the cell-mediated contraction of extracellular matrix in 3D cell-populated collagen gels. For the first time, we have confirmed significantly increased crosslinking and excessive collagen type I deposition in the clubfoot-contracted tissue. We successfully reduced these processes in vitro in a dose-dependent manner with 10-40 µg/mL of BAPN, and we observed an increasing trend in the inhibition of the cell-mediated contraction of collagen gels. The in vitro inhibitory effects indicate that BAPN has good potential for the treatment of relapsed and resistant clubfeet.

Indexed as

AminopropionitrileChild, PreschoolClubfootCollagenCross-Linking ReagentsFemaleFibroblastsHumansMaleProtein-Lysine 6-OxidaseAminopropionitrileCollagenCross-Linking ReagentsLOX protein, humanProtein-Lysine 6-Oxidasebeta-aminopropionitrile (BAPN)collagencongenital idiopathic Talipes equinovaruscontractioncrosslinkingfibrosisrelapsed clubfoot

Identifiers

PMID34769331
PMCPMC8584281
OpenAlexW3209045574

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.