Small interfering RNAs in tendon homeostasis

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Abstract

Background

Tenogenesis and tendon homeostasis are guided by genes encoding for the structural molecules of tendon fibres. Small interfering RNAs (siRNAs), acting on gene regulation, can therefore participate in the process of tendon healing.

Sources of data

A systematic search of different databases to October 2020 identified 17 suitable studies.

Areas of agreement

SiRNAs can be useful to study reparative processes of tendons and identify possible therapeutic targets in tendon healing.

Areas of controversy

Many genes and growth factors involved in the processes of tendinopathy and tendon healing can be regulated by siRNAs. It is however unclear which gene silencing determines the expected effect.

Growing points

Gene dysregulation of growth factors and tendon structural proteins can be influenced by siRNA.

Areas timely for developing research

It is not clear whether there is a direct action of the siRNAs that can be used to facilitate the repair processes of tendons.

Related collections

Most cited references 49

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Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and publication bias.

Karsten Knobloch, Uzung Yoon, Peter Vogt (2011)

Publication bias is a major problem in evidence based medicine. As well as positive outcome studies being preferentially published or followed by full text publication authors are also more likely to publish positive results in English-language journals. This unequal distribution of trials leads to a selection bias in evidence l level studies, like systematic reviews, meta-analysis or health technology assessments followed by a systematic failure of interpretation and in clinical decisions. Publication bias in a systematic review occurs mostly during the selection process and a transparent selection process is necessary to avoid such bias. For systematic reviews/meta-analysis the PRISMA-statement (formerly known as QUOROM) is recommended, as it gives the reader for a better understanding of the selection process. In the future the use of trial registration for minimizing publication bias, mechanisms to allow easier access to the scientific literature and improvement in the peer review process are recommended to overcome publication bias. The use of checklists like PRISMA is likely to improve the reporting quality of a systematic review and provides substantial transparency in the selection process of papers in a systematic review. Copyright © 2010 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

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Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments.

R Schweitzer, J Chyung, L. Murtaugh … (2001)

Little is known about the genesis and patterning of tendons and other connective tissues, mostly owing to the absence of early markers. We have found that Scleraxis, a bHLH transcription factor, is a highly specific marker for all the connective tissues that mediate attachment of muscle to bone in chick and mouse, including the limb tendons, and show that early scleraxis expression marks the progenitor cell populations for these tissues. In the early limb bud, the tendon progenitor population is found in the superficial proximomedial mesenchyme. Using the scleraxis gene as a marker we show that these progenitors are induced by ectodermal signals and restricted by bone morphogenetic protein (BMP) signaling within the mesenchyme. Application of Noggin protein antagonizes this endogenous BMP activity and induces ectopic scleraxis expression. However, the presence of excess tendon progenitors does not lead to the production of additional or longer tendons, indicating that additional signals are required for the final formation of a tendon. Finally, we show that the endogenous expression of noggin within the condensing digit cartilage contributes to the induction of distal tendons.

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Molecular mechanisms of RNA interference.

Ross Wilson, Jennifer Doudna (2013)

Small RNA molecules regulate eukaryotic gene expression during development and in response to stresses including viral infection. Specialized ribonucleases and RNA-binding proteins govern the production and action of small regulatory RNAs. After initial processing in the nucleus by Drosha, precursor microRNAs (pre-miRNAs) are transported to the cytoplasm, where Dicer cleavage generates mature microRNAs (miRNAs) and short interfering RNAs (siRNAs). These double-stranded products assemble with Argonaute proteins such that one strand is preferentially selected and used to guide sequence-specific silencing of complementary target mRNAs by endonucleolytic cleavage or translational repression. Molecular structures of Dicer and Argonaute proteins, and of RNA-bound complexes, have offered exciting insights into the mechanisms operating at the heart of RNA-silencing pathways.

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Author and article information

Journal

Title: British Medical Bulletin

Publisher: Oxford University Press (OUP)

ISSN (Print): 0007-1420

ISSN (Electronic): 1471-8391

Publication date Created: June 2021

Publication date Created: June 10 2021

Publication date Created: January 18 2021

Publication date Other: June 2021

Publication date (Print): June 10 2021

Publication date (Electronic): January 18 2021

Volume: 138

Issue: 1

Pages: 58-67

Affiliations

[1 ]Department of Trauma and Orthopaedic Surgery, AOU San Giovanni di Dio e Ruggi D’Aragona, Via San Leonardo 1, 84131 Salerno, Italy

[2 ]Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi, Italy

[3 ]Centre for Sports and Exercise Medicine, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Mile End Hospital, 275 Bancroft Road, London E1 4DG, UK

[4 ]School of Pharmacy and Bioengineering, Keele University School of Medicine, Thornburrow Drive, Stoke on Trent, UK

Article

DOI: 10.1093/bmb/ldaa040

PubMed ID: 33454750

SO-VID: a301bb50-6148-422f-bd52-053d024965ea

License:

https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

Small interfering RNAs in tendon homeostasis

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Abstract

Background

Sources of data

Areas of agreement

Areas of controversy

Growing points

Areas timely for developing research

Related collections

SAXS

Most cited references 49

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and publication bias.

Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments.

Molecular mechanisms of RNA interference.

Author and article information

Journal

Affiliations

Article

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