Characterization of Histone Modifications in Late-Stage Rotator Cuff Tendinopathy

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2023 Feb 25

PMID 36833423

Authors

Kayleigh J A Orchard

Moeed Akbar

Lindsay A N Crowe

John Cole

Neal L Millar

Stuart M Raleigh

Affiliations

Soon will be listed here.

Abstract

The development and progression of rotator cuff tendinopathy (RCT) is multifactorial and likely to manifest through a combination of extrinsic, intrinsic, and environmental factors, including genetics and epigenetics. However, the role of epigenetics in RCT, including the role of histone modification, is not well established. Using chromatin immunoprecipitation sequencing, differences in the trimethylation status of H3K4 and H3K27 histones in late-stage RCT compared to control were investigated in this study. For H3K4, 24 genomic loci were found to be significantly more trimethylated in RCT compared to control ( < 0.05), implicating genes such as , , and in RCT. For H3K27, 31 loci were shown to be more trimethylated ( < 0.05) in RCT compared to control, inferring a role for , , and . Furthermore, 14 loci were significantly less trimethylated ( < 0.05) in control compared to RCT, implicating , , and . Finally, the TGFβ signaling, axon guidance, and regulation of focal adhesion assembly pathways were found to be enriched in RCT. These findings suggest that the development and progression of RCT is, at least in part, under epigenetic control, highlighting the influence of histone modifications in this disorder and paving the way to further understand the role of epigenome in RCT.

Citing Articles

Genetic and Epigenetic Factors That Predispose to Musculoskeletal Disorders.

Raleigh S Genes (Basel). 2024; 15(9).

PMID: 39336784 PMC: 11431651. DOI: 10.3390/genes15091194.

Examining the Potential of Vitamin C Supplementation in Tissue-Engineered Equine Superficial Digital Flexor Tendon Constructs.

Mienaltowski M, Callahan M, Gonzales N, Wong A Int J Mol Sci. 2023; 24(23).

PMID: 38069418 PMC: 10707379. DOI: 10.3390/ijms242317098.

References

Langmead B, Trapnell C, Pop M, Salzberg S . Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009; 10(3):R25. PMC: 2690996. DOI: 10.1186/gb-2009-10-3-r25. View

Feng J, Liu T, Qin B, Zhang Y, Liu X . Identifying ChIP-seq enrichment using MACS. Nat Protoc. 2012; 7(9):1728-40. PMC: 3868217. DOI: 10.1038/nprot.2012.101. View

Coppens S, Barnard A, Puusepp S, Pajusalu S, Ounap K, Vargas-Franco D . A form of muscular dystrophy associated with pathogenic variants in JAG2. Am J Hum Genet. 2021; 108(5):840-856. PMC: 8206160. DOI: 10.1016/j.ajhg.2021.03.020. View

Gilbert R, Vickaryous M, Viloria-Petit A . Signalling by Transforming Growth Factor Beta Isoforms in Wound Healing and Tissue Regeneration. J Dev Biol. 2018; 4(2). PMC: 5831781. DOI: 10.3390/jdb4020021. View

Goodier H, Carr A, Snelling S, Roche L, Wheway K, Watkins B . Comparison of transforming growth factor beta expression in healthy and diseased human tendon. Arthritis Res Ther. 2016; 18:48. PMC: 4756520. DOI: 10.1186/s13075-016-0947-8. View

Hartmann S, Ridley A, Lutz S . The Function of Rho-Associated Kinases ROCK1 and ROCK2 in the Pathogenesis of Cardiovascular Disease. Front Pharmacol. 2015; 6:276. PMC: 4653301. DOI: 10.3389/fphar.2015.00276. View

Huang D, Sherman B, Lempicki R . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2008; 37(1):1-13. PMC: 2615629. DOI: 10.1093/nar/gkn923. View

Quinlan A, Hall I . BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010; 26(6):841-2. PMC: 2832824. DOI: 10.1093/bioinformatics/btq033. View

Longo U, Candela V, Berton A, Salvatore G, Guarnieri A, DeAngelis J . Genetic basis of rotator cuff injury: a systematic review. BMC Med Genet. 2019; 20(1):149. PMC: 6720871. DOI: 10.1186/s12881-019-0883-y. View

10.

Plachel F, Heuberer P, Gehwolf R, Frank J, Tempfer H, Lehner C . MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies. J Orthop Res. 2019; 38(1):202-211. PMC: 6973295. DOI: 10.1002/jor.24473. View

11.

de Lima J, Bonnin M, Birchmeier C, Duprez D . Muscle contraction is required to maintain the pool of muscle progenitors via YAP and NOTCH during fetal myogenesis. Elife. 2016; 5. PMC: 5030091. DOI: 10.7554/eLife.15593. View

12.

Motta G, Amaral M, Rezende E, Pitta R, Vieira T, Duarte M . Evidence of genetic variations associated with rotator cuff disease. J Shoulder Elbow Surg. 2013; 23(2):227-35. DOI: 10.1016/j.jse.2013.07.053. View

13.

Liu J, Tao X, Chen L, Han W, Zhou Y, Tang K . CTGF positively regulates BMP12 induced tenogenic differentiation of tendon stem cells and signaling. Cell Physiol Biochem. 2015; 35(5):1831-45. DOI: 10.1159/000373994. View

14.

Elineni K, Gallant N . Regulation of cell adhesion strength by peripheral focal adhesion distribution. Biophys J. 2012; 101(12):2903-11. PMC: 3244064. DOI: 10.1016/j.bpj.2011.11.013. View

15.

Gallo MacFarlane E, Haupt J, Dietz H, Shore E . TGF-β Family Signaling in Connective Tissue and Skeletal Diseases. Cold Spring Harb Perspect Biol. 2017; 9(11). PMC: 5666637. DOI: 10.1101/cshperspect.a022269. View

16.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

17.

Afgan E, Baker D, Batut B, van den Beek M, Bouvier D, cech M . The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic Acids Res. 2018; 46(W1):W537-W544. PMC: 6030816. DOI: 10.1093/nar/gky379. View

18.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

19.

Bolger A, Lohse M, Usadel B . Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014; 30(15):2114-20. PMC: 4103590. DOI: 10.1093/bioinformatics/btu170. View

20.

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View