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Arthritis Research & Therapy

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Open Access 01-12-2015 | Research article

Transcriptome analysis of ageing in uninjured human Achilles tendon

Authors: Mandy Jayne Peffers, Yongxiang Fang, Kathleen Cheung, Tim Koh Jia Wei, Peter David Clegg, Helen Lucy Birch

Published in: Arthritis Research & Therapy | Issue 1/2015

Abstract

Introduction

The risk of tendon injury and disease increases significantly with increasing age. The aim of the study was to characterise transcriptional changes in human Achilles tendon during the ageing process in order to identify molecular signatures that might contribute to age-related degeneration.

Methods

RNA for gene expression analysis using RNA-Seq and quantitative real-time polymerase chain reaction analysis was isolated from young and old macroscopically normal human Achilles tendon. RNA sequence libraries were prepared following ribosomal RNA depletion, and sequencing was undertaken by using the Illumina HiSeq 2000 platform. Expression levels among genes were compared by using fragments per kilobase of exon per million fragments mapped. Differentially expressed genes were defined by using Benjamini-Hochberg false discovery rate approach (P <0.05, expression ratios 1.4 log₂ fold change). Alternative splicing of exon variants were also examined by using Cufflinks. The functional significance of genes that showed differential expression between young and old tendon was determined by using ingenuity pathway analysis.

Results

In total, the expression of 325 transcribed elements, including protein-coding transcripts and non-coding transcripts (small non-coding RNAs, pseudogenes, long non-coding RNAs and a single microRNA), was significantly different in old compared with young tendon (±1.4 log₂ fold change, P <0.05). Of these, 191 were at higher levels in older tendon and 134 were at lower levels in older tendon. The top networks for genes differentially expressed with tendon age were from cellular function, cellular growth, and cellular cycling pathways. Notable differential transcriptome changes were also observed in alternative splicing patterns. Several of the top gene ontology terms identified in downregulated isoforms in old tendon related to collagen and post-translational modification of collagen.

Conclusions

This study demonstrates dynamic alterations in RNA with age at numerous genomic levels, indicating changes in the regulation of transcriptional networks. The results suggest that ageing is not primarily associated with loss of ability to synthesise matrix proteins and matrix-degrading enzymes. In addition, we have identified non-coding RNA genes and differentially expressed transcript isoforms of known matrix components with ageing which require further investigation.

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Beard JR, Biggs S, Bloom BD, Fried LP, Hogan L, Kalache A, et al. Global Population Ageing: Peril or Promise. Geneva: World Economic Forum; 2011.

Clayton RA, Court-Brown CM. The epidemiology of musculoskeletal tendinous and ligamentous injuries. Injury. 2008;39:1338–44.CrossRefPubMed

Hess GW. Achilles tendon rupture: a review of etiology, population, anatomy, risk factors, and injury prevention. Foot Ankle Spec. 2010;3:29–32.CrossRefPubMed

Movin T, Gad A, Reinholt FP, Rolf C. Tendon pathology in long-standing achillodynia. Biopsy findings in 40 patients. Acta Orthop Scand. 1997;68:170–5.CrossRefPubMed

Corps AN, Robinson AH, Harrall RL, Avery NC, Curry VA, Hazleman BL, et al. Changes in matrix protein biochemistry and the expression of mRNA encoding matrix proteins and metalloproteinases in posterior tibialis tendinopathy. Ann Rheum Dis. 2012;71:746–52.CrossRefPubMedCentralPubMed

Riley GP, Goddard MJ, Hazleman BL. Histopathological assessment and pathological significance of matrix degeneration in supraspinatus tendons. Rheumatology (Oxford). 2001;40:229–30.CrossRef

Birch HL, Bailey AJ, Goodship AE. Macroscopic 'degeneration' of equine superficial digital flexor tendon is accompanied by a change in extracellular matrix composition. Equine Vet J. 1998;30:534–9.CrossRefPubMed

Tavernarakis N. Ageing and the regulation of protein synthesis: a balancing act? Trends Cell Biol. 2008;18:228–35.CrossRefPubMed

Rodier F, Campisi J. Four faces of cellular senescence. J Cell Biol. 2011;192:547–56.CrossRefPubMedCentralPubMed

10.

Riley G. Tendinopathy–from basic science to treatment. Nat Clin Pract Rheumatol. 2008;4:82–9.CrossRefPubMed

11.

Thorpe CT, Streeter I, Pinchbeck GL, Goodship AE, Clegg PD, Birch HL. Aspartic acid racemization and collagen degradation markers reveal an accumulation of damage in tendon collagen that is enhanced with aging. J Biol Chem. 2010;285:15674–81.CrossRefPubMedCentralPubMed

12.

Dudhia J, Scott CM, Draper ER, Heinegard D, Pitsillides AA, Smith RK. Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell. 2007;6:547–56.CrossRefPubMed

13.

Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.CrossRefPubMed

14.

Dakin SG, Dudhia J, Werling NJ, Werling D, Abayasekara DR, Smith RK. Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease. PLoS One. 2012;7:e48978.CrossRefPubMedCentralPubMed

15.

Kirkwood TB. A systematic look at an old problem. Nature. 2008;451:644–7.CrossRefPubMed

16.

Molloy TJ, Wang Y, Horner A, Skerry TM, Murrell GA. Microarray analysis of healing rat Achilles tendon: evidence for glutamate signaling mechanisms and embryonic gene expression in healing tendon tissue. J Orthop Res. 2006;24:842–55.CrossRefPubMed

17.

Molloy TJ, Kemp MW, Wang Y, Murrell GA. Microarray analysis of the tendinopathic rat supraspinatus tendon: glutamate signaling and its potential role in tendon degeneration. J Appl Physiol. 2006;101:1702–9.CrossRefPubMed

18.

Maeda E, Fleischmann C, Mein CA, Shelton JC, Bader DL, Lee DA. Functional analysis of tenocytes gene expression in tendon fascicles subjected to cyclic tensile strain. Connect Tissue Res. 2010;51:434–44.CrossRefPubMed

19.

Eliasson P, Andersson T, Aspenberg P. Influence of a single loading episode on gene expression in healing rat Achilles tendons. J Appl Physiol (1985). 2012;112:279–88.

20.

Eliasson P, Andersson T, Hammerman M, Aspenberg P. Primary gene response to mechanical loading in healing rat Achilles tendons. J Appl Physiol (1985). 2013;114:1519–26.

21.

Troy A, Sharpless NE. Genetic ‘lnc’-age of noncoding RNAs to human disease. J Clin Invest. 2012;122:3837–40.CrossRefPubMedCentralPubMed

22.

Abdelmohsen K, Panda A, Kang MJ, Xu J, Selimyan R, Yoon JH, et al. Senescence-associated lncRNAs: senescence-associated long noncoding RNAs. Aging Cell. 2013;12:890–900.CrossRefPubMedCentralPubMed

23.

Kato M, Slack FJ. Ageing and the small, non-coding RNA world. Ageing Res Rev. 2013;12:429–35.CrossRefPubMedCentralPubMed

24.

Peffers MJ, Liu X, Clegg PD. Transcriptomic signatures in cartilage ageing. Arthritis Res Ther. 2013;15:R98.CrossRefPubMedCentralPubMed

25.

Peffers MJ, Beynon RJ, Clegg PD. Absolute quantification of selected proteins in the human osteoarthritic secretome. Int J Mol Sci. 2013;14:20658–81.CrossRefPubMedCentralPubMed

26.

Martin M. Cutadapt removes adapter sequences from high through put sequencing reads. EMB Net J. 2011;17:10–2.CrossRef

27.

Human reference genome sequence. ftp://ftp.ensembl.org/pub/release-73/fasta/homo_sapiens/dna/. 2014.

28.

Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013;14:R36.CrossRefPubMedCentralPubMed

29.

Human genome annotation. ftp://ftp.ensembl.org/pub/release-73/gtf/homo_sapiens/. 2014.

30.

Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26:139–40.CrossRefPubMedCentralPubMed

31.

Benjamini Y, Hochberg Y. Controlling the false discovery rate - a practical and powerful approach to multiple testing. J Roy Stat Soc B Met. 1995;57:289–300.

32.

Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9:357–9.CrossRefPubMedCentralPubMed

33.

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25:2078–9.CrossRefPubMedCentralPubMed

34.

Picard, a set of Java command line tools for manipulating high-throughput sequencing. http://broadinstitute.github.io/picard/. 2014.

35.

Trapnell C, Pachter L, Salzberg SL. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009;25:1105–11.CrossRefPubMedCentralPubMed

36.

Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7:562–78.CrossRefPubMedCentralPubMed

37.

Wickham H, editor. ggplot2: elegant graphics for data analysis. New York: Springer; 2009.

38.

Ingenuity systems. Ingenuity pathway analysis. http://www.ingenuity.com. 2014.

39.

Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.CrossRef

40.

Martin I, Jakob M, Schafer D, Dick W, Spagnoli G, Heberer M. Quantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints. Osteoarthritis Cartilage. 2001;9:112–8.CrossRefPubMed

41.

Noh EM, Kim JS, Hur H, Park BH, Song EK, Han MK, et al. Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts. Rheumatology. 2009;48:45–8.CrossRefPubMed

42.

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3:RESEARCH0034.

43.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25:402–8.CrossRefPubMed

44.

Ewing B, Hillier L, Wendl MC, Green P. Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res. 1998;8:175–85.CrossRefPubMed

45.

Marioni JC, Mason CE, Mane SM, Stephens M, Gilad Y. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res. 2008;18:1509–17.CrossRefPubMedCentralPubMed

46.

A software system which produces and maintains automatic annotation on selected eukaryotic genomes. http://www.ensemble.org. 2014.

47.

A repository for high-quality gene models produced by the manual annotation of vertebrate genomes. http://vega.sanger.ac.uk/.

48.

Corps AN, Robinson AH, Movin T, Costa ML, Ireland DC, Hazleman BL, et al. Versican splice variant messenger RNA expression in normal human Achilles tendon and tendinopathies. Rheumatology. 2004;43:969–72.CrossRefPubMed

49.

Legerlotz K, Jones ER, Screen HR, Riley GP. Increased expression of IL-6 family members in tendon pathology. Rheumatology (Oxford). 2012;51:1161–5.CrossRef

50.

Jelinsky SA, Rodeo SA, Li J, Gulotta LV, Archambault JM, Seeherman HJ. Regulation of gene expression in human tendinopathy. BMC Musculoskelet Disord. 2011;12:86.CrossRefPubMedCentralPubMed

51.

Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM, et al. Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon. Arthritis Rheum. 2006;54:832–42.CrossRefPubMed

52.

Archambault JM, Jelinsky SA, Lake SP, Hill AA, Glaser DL, Soslowsky LJ. Rat supraspinatus tendon expresses cartilage markers with overuse. J Orthop Res. 2007;25:617–24.CrossRefPubMed

53.

Birch HL, Bailey JV, Bailey AJ, Goodship AE. Age-related changes to the molecular and cellular components of equine flexor tendons. Equine Vet J. 1999;31:391–6.CrossRefPubMed

54.

Thorpe CT, Birch HL, Clegg PD, Screen HR. The role of the non-collagenous matrix in tendon function. Int J Exp Pathol. 2013;94:248–59.CrossRefPubMedCentralPubMed

55.

Peffers MJ, Thorpe CT, Collins JA, Eong R, Wei TK, Screen HR, et al. Proteomic analysis reveals Age-related changes in tendon matrix composition, with Age- and injury-specific matrix fragmentation. J Biol Chem. 2014;289:25867–78.CrossRefPubMedCentralPubMed

56.

Faria A, Gabriel R, Abrantes J, Bras R, Moreira H. Biomechanical properties of the triceps surae muscle-tendon unit in young and postmenopausal women. Clin Biomech (Bristol, Avon). 2011;26:523–28.

57.

Thermann H, Frerichs O, Biewener A, Krettek C, Schandelmaier P. Biomechanical studies of human Achilles tendon rupture. Unfallchirurg. 1995;98:570–5.PubMed

58.

Kubo K, Kanehisa H, Miyatani M, Tachi M, Fukunaga T. Effect of low-load resistance training on the tendon properties in middle-aged and elderly women. Acta Physiol Scand. 2003;178:25–32.CrossRefPubMed

59.

Magnusson SP, Narici MV, Maganaris CN, Kjaer M. Human tendon behaviour and adaptation, in vivo. J Physiol. 2008;586:71–81.CrossRefPubMedCentralPubMed

60.

Kohler J, Popov C, Klotz B, Alberton P, Prall WC, Haasters F, et al. Uncovering the cellular and molecular changes in tendon stem/progenitor cells attributed to tendon aging and degeneration. Aging Cell. 2013;12:988–99.CrossRefPubMedCentralPubMed

61.

Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, et al. Alternative isoform regulation in human tissue transcriptomes. Nature. 2008;456:470–6.CrossRefPubMedCentralPubMed

62.

Stamm S, Ben-Ari S, Rafalska I, Tang Y, Zhang Z, Toiber D, et al. Function of alternative splicing. Gene. 2005;344:1–20.CrossRefPubMed

63.

Sun Y, Berger EJ, Zhao C, Jay GD, An KN, Amadio PC. Expression and mapping of lubricin in canine flexor tendon. J Orthop Res. 2006;24:1861–8.CrossRefPubMed

64.

Heinemeier KM, Olesen JL, Schjerling P, Haddad F, Langberg H, Baldwin KM, et al. Short-term strength training and the expression of myostatin and IGF-I isoforms in rat muscle and tendon: differential effects of specific contraction types. J Appl Physiol (1985). 2007;102:573–81.

65.

Hato T, Tabata M, Oike Y. The role of angiopoietin-like proteins in angiogenesis and metabolism. Trends Cardiovasc Med. 2008;18:6–14.CrossRefPubMed

66.

Xu A, Lam MC, Chan KW, Wang Y, Zhang J, Hoo RL, et al. Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice. Proc Natl Acad Sci U S A. 2005;102:6086–91.CrossRefPubMedCentralPubMed

67.

Ono M, Shimizugawa T, Shimamura M, Yoshida K, Noji-Sakikawa C, Ando Y, et al. Protein region important for regulation of lipid metabolism in angiopoietin-like 3 (ANGPTL3): ANGPTL3 is cleaved and activated in vivo. J Biol Chem. 2003;278:41804–9.CrossRefPubMed

68.

Peek R, Kammerer RA, Frank S, Otte-Holler I, Westphal JR. The angiopoietin-like factor cornea-derived transcript 6 is a putative morphogen for human cornea. J Biol Chem. 2002;277:686–93.CrossRefPubMed

69.

Comes N, Buie LK, Borras T. Evidence for a role of angiopoietin-like 7 (ANGPTL7) in extracellular matrix formation of the human trabecular meshwork: implications for glaucoma. Genes Cells. 2011;16:243–59.CrossRefPubMedCentralPubMed

70.

Pincus Z, Slack FJ. Transcriptional (dys)regulation and aging in Caenorhabditis elegans. Genome Biol. 2008;9:233.CrossRefPubMedCentralPubMed

71.

Bodyak N, Kang PM, Hiromura M, Sulijoadikusumo I, Horikoshi N, Khrapko K, et al. Gene expression profiling of the aging mouse cardiac myocytes. Nucleic Acids Res. 2002;30:3788–94.CrossRefPubMedCentralPubMed

72.

Lu T, Aron L, Zullo J, Pan Y, Kim H, Chen Y, et al. REST and stress resistance in ageing and Alzheimer's disease. Nature. 2014;507:448–54.CrossRefPubMedCentralPubMed

73.

Satoh A, Imai S. Hypothalamic Sirt1 in aging. Aging (Albany NY). 2014;6:1–2.

74.

Brent AE, Schweitzer R, Tabin CJ. A somitic compartment of tendon progenitors. Cell. 2003;113:235–48.CrossRefPubMed

75.

Guerquin MJ, Charvet B, Nourissat G, Havis E, Ronsin O, Bonnin MA, et al. Transcription factor EGR1 directs tendon differentiation and promotes tendon repair. J Clin Invest. 2013;123:3564–76.CrossRefPubMedCentralPubMed

76.

Gross G, Hoffmann A. Therapeutic strategies for tendon healing based on novel biomaterials, factors and cells. Pathobiology. 2013;80:203–10.CrossRefPubMed

77.

Rapicavoli NA, Qu K, Zhang J, Mikhail M, Laberge RM, Chang HY. A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics. Elife. 2013;2:e00762.CrossRefPubMedCentralPubMed

78.

Baker M. Long noncoding RNAs: the search for function. Nat Methods. 2011;8:379–83.CrossRef

79.

Lukiw WJ, Handley P, Wong L, Crapper McLachlan DR. BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD). Neurochem Res. 1992;17:591–7.CrossRefPubMed

80.

Liu Q, Zhang X, Dai L, Hu X, Zhu J, Li L, et al. Long noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritis. Arthritis Rheum. 2013;66:969–78.CrossRef

81.

Steck E, Boeuf S, Gabler J, Werth N, Schnatzer P, Diederichs S, et al. Regulation of H19 and its encoded microRNA-675 in osteoarthritis and under anabolic and catabolic in vitro conditions. J Mol Med (Berl). 2012;90:1185–95.CrossRef

82.

Barter MJ, Hyatt S, Xu Y, Young DA. Long non-coding RNAs in osteoarthritis and chondrogenesis. Osteoarthritis Cartilage. 2014;22(Supplement):S222.

83.

Neguembor MV, Jothi M, Gabellini D. Long noncoding RNAs, emerging players in muscle differentiation and disease. Skelet Muscle. 2014;4:8.CrossRefPubMedCentralPubMed

84.

Li JP, Liu LH, Li J, Chen Y, Jiang XW, Ouyang YR, et al. Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun. 2013;433:200–6.CrossRefPubMed

Title: Transcriptome analysis of ageing in uninjured human Achilles tendon
Authors: Mandy Jayne Peffers
Yongxiang Fang
Kathleen Cheung
Tim Koh Jia Wei
Peter David Clegg
Helen Lucy Birch
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 1/2015
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/s13075-015-0544-2

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Abstract

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