The role of miRNA and lncRNA in heterotopic ossification pathogenesis

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Abstract

Heterotopic ossification (HO) is the formation of bone in non-osseous tissues, such as skeletal muscles. The HO could have a genetic or a non-genetic (acquired) background, that is, it could be caused by musculoskeletal trauma, such as burns, fractures, joint arthroplasty (traumatic HO), or cerebral or spinal insult (neurogenetic HO). HO formation is caused by the differentiation of stem or progenitor cells induced by local or systemic imbalances. The main factors described so far in HO induction are TGFβ1, BMPs, activin A, oncostatin M, substance P, neurotrophin-3, and WNT. In addition, dysregulation of noncoding RNAs, such as microRNA or long noncoding RNA, homeostasis may play an important role in the development of HO. For example, decreased expression of miRNA-630, which is responsible for the endothelial–mesenchymal transition, was observed in HO patients. The reduced level of miRNA-421 in patients with humeral fracture was shown to be associated with overexpression of BMP2 and a higher rate of HO occurrence. Down-regulation of miRNA-203 increased the expression of runt-related transcription factor 2 ( RUNX2), a crucial regulator of osteoblast differentiation. Thus, understanding the various functions of noncoding RNAs can reveal potential targets for the prevention or treatment of HO.

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MicroRNAs: genomics, biogenesis, mechanism, and function.

David Bartel (2004)

MicroRNAs (miRNAs) are endogenous approximately 22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.

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Is Open Access

Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

Jacob O'Brien, Heyam Hayder, Yara Zayed … (2018)

MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.

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Metazoan MicroRNAs

David Bartel (2018)

MicroRNAs (miRNAs) are ∼22 nt RNAs that direct posttranscriptional repression of mRNA targets in diverse eukaryotic lineages. In humans and other mammals, these small RNAs help sculpt the expression of most mRNAs. This article reviews advances in our understanding of the defining features of metazoan miRNAs and their biogenesis, genomics, and evolution. It then reviews how metazoan miRNAs are regulated, how they recognize and cause repression of their targets, and the biological functions of this repression, with a compilation of knockout phenotypes that shows that important biological functions have been identified for most of the broadly conserved miRNAs of mammals.

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Author and article information

Contributors

Łukasz Pulik:

ORCID: http://orcid.org/0000-0002-4953-0075

lpulik@wum.edu.pl

Journal

Journal ID (nlm-ta): Stem Cell Res Ther

Journal ID (iso-abbrev): Stem Cell Res Ther

Title: Stem Cell Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-6512

Publication date (Electronic): 15 December 2022

Publication date PMC-release: 15 December 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 523

Affiliations

[1 ]GRID grid.13339.3b, ISNI 0000000113287408, Department of Orthopaedics and Traumatology, , Medical University of Warsaw, ; Lindley 4 St, 02-005 Warsaw, Poland

[2 ]GRID grid.12847.38, ISNI 0000 0004 1937 1290, Department of Cytology, Faculty of Biology, , University of Warsaw, ; Miecznikowa 1 St, 02-096 Warsaw, Poland

Author information

Łukasz Pulik http://orcid.org/0000-0002-4953-0075

Article

Publisher ID: 3213

DOI: 10.1186/s13287-022-03213-3

PMC ID: 9753082

PubMed ID: 36522666

SO-VID: 348578ea-d3de-4c70-bb39-c1a2ea89f4c2

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Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 18 May 2022

Date accepted : 6 December 2022

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ScienceOpen disciplines: Molecular medicine

Keywords: heterotopic ossification,noncoding rnas,microrna,long noncoding rna

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ScienceOpen disciplines: Molecular medicine

Keywords: heterotopic ossification, noncoding rnas, microrna, long noncoding rna

The role of miRNA and lncRNA in heterotopic ossification pathogenesis

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Most cited references 200

MicroRNAs: genomics, biogenesis, mechanism, and function.

Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

Metazoan MicroRNAs

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