Conjoint analysis of lncRNA and mRNA expression in rotator cuff tendinopathy

Ge, Zilu; Tang, Hong; Lyu, Jingtong; Zhou, Binghua; Yang, Mingyu; Tang, Kanglai; Chen, Wan

doi:10.21037/atm.2020.02.149

Cited by 16 publications

(25 citation statements)

References 39 publications

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“…The functions of miRNAs in tendinopathy are a topic of intense investigation, but the role of lncRNAs remains largely obscure. 39 , 40 Mandy and colleagues used deep sequencing of transcriptome analysis to identify that several lncRNAs are changed in uninjured human Achilles tendon, leaving their functions to be further explored. 41 Also, several lncRNAs have been identified from analysis of transcriptomic data from tissue-engineered tendons.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling

et al. 2021

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Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling

et al. 2021

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“…Currently, few human studies have characterized gene expression in RC muscle after tendon tear and how it relates to the severity of muscle changes (Reardon et al, 2001;Steinbacher et al, 2010;Choo et al, 2014;Chaudhury et al, 2016;Shah et al, 2017;Gibbons et al, 2018a;Ren et al, 2018;Ge et al, 2020;Tashjian et al, 2020), but these data could not be related to a time course neither compared to a healthy control. Gene expression data with two or more time points have been collected in a mouse RC tear model and a rat tenotomy and neurectomy model (Lee et al, 2018;Gumucio et al, 2019;Hu et al, 2019), typically focusing on specific programs and gene overlap over the time series.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Time Course After Rotator Cuff Tear

et al. 2021

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Rotator cuff (RC) tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration in the chronic state, which is not improved with intervention or surgical repair. This highlights the need to better understand the underlying dysfunction in muscle after RC tendon tear. Contemporary studies aimed at understanding muscle pathobiology after RC tear have considered transcriptional data in mice, rats and sheep models at 2–3 time points (1 to 16 weeks post injury). However, none of these studies observed a transition or resurgence of gene expression after the initial acute time points. In this study, we collected rabbit supraspinatus muscle tissue with high temporal resolution (1, 2, 4, 8, and 16 weeks) post-tenotomy (n = 6/group), to determine if unique, time-dependent transcriptional changes occur. RNA sequencing and analyses were performed to identify a transcriptional timeline of RC muscle changes and related morphological sequelae. At 1-week post-tenotomy, the greatest number of differentially expressed genes was observed (1,069 up/873 down) which decreases through 2 (170/133), 4 (86/41), and 8 weeks (16/18), followed by a resurgence and transition of expression at 16 weeks (1,421/293), a behavior which previously has not been captured or reported. Broadly, 1-week post-tenotomy is an acute time point with expected immune system responses, catabolism, and changes in energy metabolism, which continues into 2 weeks with less intensity and greater contribution from mitochondrial effects. Expression shifts at 4 weeks post-tenotomy to fatty acid oxidation, lipolysis, and general upregulation of adipogenesis related genes. The effects of previous weeks’ transcriptional dysfunction present themselves at 8 weeks post-tenotomy with enriched DNA damage binding, aggresome activity, extracellular matrix-receptor changes, and significant expression of genes known to induce apoptosis. At 16 weeks post-tenotomy, there is a range of enriched pathways including extracellular matrix constituent binding, mitophagy, neuronal activity, immune response, and more, highlighting the chaotic nature of this time point and possibility of a chronic classification. Transcriptional activity correlated significantly with histological changes and were enriched for biologically relevant pathways such as lipid metabolism. These data provide platform for understanding the biological mechanisms of chronic muscle degeneration after RC tears.

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“…Both snap‐frozen and fresh tissue can be used for bulk transcriptomics (Table 2). Snap‐frozen bulk transcriptomics have been previously used on human, 37 murine, 17 rat, 38 and equine 34 tendons (Table 2). For frozen samples, usually disruption and homogenization of the tissue is necessary before RNA isolation.…”

Section: Rna Extraction and Transcriptome Sequencingmentioning

confidence: 99%

Research perspectives—Pipelines to human tendon transcriptomics

Ramos‐Mucci

Sarmiento

Little

et al. 2022

Journal Orthopaedic Research

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Tendon transcriptomics is a rapidly growing field in musculoskeletal biology. The ultimate aim of many current tendon transcriptomic studies is characterization of in vitro, ex vivo, or in vivo, healthy, and diseased tendon microenvironments to identify the underlying pathways driving human tendon pathology. The transcriptome interfaces between genomic, proteomic, and metabolomic signatures of the tendon cellular niche and the response of this niche to stimuli. Some of the greatest bottlenecks in tendon transcriptomics relate to the availability and quality of human tendon tissue, hence animal tissues are frequently used even though human tissue is most translationally relevant. Here, we review the variability associated with human donor and procurement factors, such as whether the tendon is cadaveric or a clinical remnant, and how these variables affect the quality and relevance of the transcriptomes obtained. Moreover, age, sex, and health demographic variables impact the human tendon transcriptome. Tendons present tissue‐specific challenges for cell, nuclei, and RNA extraction that include a dense extracellular matrix, low cellularity, and therefore low RNA yield of variable quality. Consideration of these factors is particularly important for single‐cell and single‐nuclei resolution transcriptomics due to the necessity for unbiased and representative cell or nuclei populations. Different cell, nuclei, and RNA extraction methods, library preparation, and quality control methods are used by the tendon research community and attention should be paid to these when designing and reporting studies. We discuss the different components and challenges of human tendon transcriptomics, and propose pipelines, quality control, and reporting guidelines for future work in the field.

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Conjoint analysis of lncRNA and mRNA expression in rotator cuff tendinopathy

Cited by 16 publications

References 39 publications

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling

Transcriptional Time Course After Rotator Cuff Tear

Research perspectives—Pipelines to human tendon transcriptomics

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