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BMC musculoskeletal disorders2009; 10; 27; doi: 10.1186/1471-2474-10-27

Gene expression markers of tendon fibroblasts in normal and diseased tissue compared to monolayer and three dimensional culture systems.

Abstract: There is a paucity of data regarding molecular markers that identify the phenotype of the tendon cell. This study aims to quantify gene expression markers that distinguish between tendon fibroblasts and other mesenchymal cells which may be used to investigate tenogenesis. Methods: Expression levels for 12 genes representative of musculoskeletal tissues, including the proposed tendon progenitor marker scleraxis, relative to validated reference genes, were evaluated in matched samples of equine tendon (harvested from the superficial digital flexor tendon), cartilage and bone using quantitative PCR (qPCR). Expression levels of genes associated with tendon phenotype were then evaluated in healthy, including developmental, and diseased equine tendon tissue and in tendon fibroblasts maintained in both monolayer culture and in three dimensional (3D) collagen gels. Results: Significantly increased expression of scleraxis was found in tendon compared with bone (P = 0.002) but not compared to cartilage. High levels of COL1A2 and scleraxis and low levels of tenascin-C were found to be most representative of adult tensional tendon phenotype. While, relative expression of scleraxis in developing mid-gestational tendon or in acute or chronically diseased tendon did not differ significantly from normal adult tendon, tenascin-C message was significantly upregulated in acutely injured equine tendon (P = 0.001). Relative scleraxis gene expression levels in tendon cell monolayer and 3D cultures were significantly lower than in normal adult tendon (P = 0.002, P = 0.02 respectively). Conclusions: The findings of this study indicate that high expression of both COL1A2 and scleraxis, and low expression of tenascin-C is representative of a tensional tendon phenotype. The in vitro culture methods used in these experiments however, may not recapitulate the phenotype of normal tensional tendon fibroblasts in tissues as evidenced by gene expression.
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Publication Date: 2009-02-26 PubMed ID: 19245707PubMed Central: PMC2651848DOI: 10.1186/1471-2474-10-27Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on exploring gene expression markers that differentiate tendon fibroblasts from other similar cells. The study conducted experiments to analyze the expression levels of certain genes in samples procured from equine tissues. The findings suggest high expression of COL1A2 and scleraxis, and low expression of tenascin-C indicate a tensional tendon phenotype. However, in vitro culture methods used in the study may not fully replicate the actual behavior of these cells in tissues.

Objective of the Study

  • The main goal of this study was to identify and quantify gene expression markers that distinguish tendon fibroblasts from other mesenchymal cells.
  • By doing so, the researchers hoped to contribute more information that could be used to study tenogenesis, a term describing the formation and development of tendons.

Methods Adopted

  • Expression levels of 12 genes representative of musculoskeletal tissues were evaluated. Among these was the proposed tendon progenitor marker, scleraxis.
  • The evaluation was conducted on samples of equine tendon, cartilage, and bone, using a method called quantitative PCR (qPCR).
  • The study then investigated gene expression levels associated with tendon phenotype in healthy, developing, and diseased equine tendon tissue.
  • Experiments also included studying tendon fibroblasts maintained in both monolayer culture and in three-dimensional (3D) collagen gels.

Study Results

  • The analysis revealed a significant increase in scleraxis expression in tendon compared to bone, but no substantial difference was found when compared to cartilage.
  • In terms of representing an adult tendon phenotype, high levels of COL1A2 and scleraxis and low levels of tenascin-C were found to be the most indicative.
  • Furthermore, the expression of the scleraxis gene in developing or diseased tendons did not significantly differ from its expression in normal tendons.
  • Contrastingly, tenascin-C expression was significantly higher in tendons with acute injuries.
  • Relative to normal adult tendon, scleraxis gene expression levels in tendon cell monolayer and 3D cultures were significantly lower.

Study Conclusions

  • The study concludes that a high expression of COL1A2 and scleraxis, coupled with a low expression of tenascin-C, is representative of a tensional tendon phenotype.
  • However, the researchers also noted that the in vitro culture methods they employed may not accurately represent the phenotype of normal tensional tendon fibroblasts in tissue, as indicated by disparities in the gene expression.

Cite This Article

APA
Taylor SE, Vaughan-Thomas A, Clements DN, Pinchbeck G, Macrory LC, Smith RK, Clegg PD. (2009). Gene expression markers of tendon fibroblasts in normal and diseased tissue compared to monolayer and three dimensional culture systems. BMC Musculoskelet Disord, 10, 27. https://doi.org/10.1186/1471-2474-10-27

Publication

BMC musculoskeletal disorders
ISSN: 1471-2474
NlmUniqueID: 100968565
Country: England
Language: English
Volume: 10
Pages: 27

Researcher Affiliations

Taylor, Sarah E
  • Department of Veterinary Clinical Science, University of Liverpool, Neston, South Wirral, UK. Sarah.Taylor@liv.ac.uk
Vaughan-Thomas, Anne
    Clements, Dylan N
      Pinchbeck, Gina
        Macrory, Lisa C
          Smith, Roger K W
            Clegg, Peter D

              MeSH Terms

              • Animals
              • Basic Helix-Loop-Helix Transcription Factors / genetics
              • Basic Helix-Loop-Helix Transcription Factors / metabolism
              • Cartilage, Articular / metabolism
              • Cartilage, Articular / pathology
              • Cell Culture Techniques / methods
              • Collagen / metabolism
              • Fibroblasts / metabolism
              • Fibroblasts / pathology
              • Gels
              • Gene Expression
              • Genetic Markers
              • Horses
              • Metacarpal Bones / metabolism
              • Metacarpal Bones / pathology
              • Tendinopathy / metabolism
              • Tendinopathy / pathology
              • Tendons / metabolism
              • Tendons / pathology

              References

              This article includes 48 references
              1. McCormick A, Charlton J, Fleming D. Assessing health needs in primary care. Morbidity study from general practice provides another source of information.. BMJ 1995 Jun 10;310(6993):1534.
                pmc: PMC2549904pubmed: 7787617doi: 10.1136/bmj.310.6993.1534dgoogle scholar: lookup
              2. Dowling BA, Dart AJ, Hodgson DR, Smith RK. Superficial digital flexor tendonitis in the horse.. Equine Vet J 2000 Sep;32(5):369-78.
                doi: 10.2746/042516400777591138pubmed: 11037257google scholar: lookup
              3. Kasashima Y, Takahashi T, Smith RK, Goodship AE, Kuwano A, Ueno T, Hirano S. Prevalence of superficial digital flexor tendonitis and suspensory desmitis in Japanese Thoroughbred flat racehorses in 1999.. Equine Vet J 2004 May;36(4):346-50.
                doi: 10.2746/0425164044890580pubmed: 15163043google scholar: lookup
              4. Patterson-Kane JC, Firth EC. The pathobiology of exercise-induced superficial digital flexor tendon injury in Thoroughbred racehorses.. Vet J 2009 Aug;181(2):79-89.
                pubmed: 18406184doi: 10.1016/j.tvjl.2008.02.009google scholar: lookup
              5. Wang JH. Mechanobiology of tendon.. J Biomech 2006;39(9):1563-82.
                doi: 10.1016/j.jbiomech.2005.05.011pubmed: 16000201google scholar: lookup
              6. Dyson SJ. Medical management of superficial digital flexor tendonitis: a comparative study in 219 horses (1992-2000).. Equine Vet J 2004 Jul;36(5):415-9.
                doi: 10.2746/0425164044868422pubmed: 15253082google scholar: lookup
              7. Richardson LE, Dudhia J, Clegg PD, Smith R. Stem cells in veterinary medicine--attempts at regenerating equine tendon after injury.. Trends Biotechnol 2007 Sep;25(9):409-16.
                doi: 10.1016/j.tibtech.2007.07.009pubmed: 17692415google scholar: lookup
              8. Riley G. Tendinopathy--from basic science to treatment.. Nat Clin Pract Rheumatol 2008 Feb;4(2):82-9.
                doi: 10.1038/ncprheum0700pubmed: 18235537google scholar: lookup
              9. Butler DL, Juncosa-Melvin N, Boivin GP, Galloway MT, Shearn JT, Gooch C, Awad H. Functional tissue engineering for tendon repair: A multidisciplinary strategy using mesenchymal stem cells, bioscaffolds, and mechanical stimulation.. J Orthop Res 2008 Jan;26(1):1-9.
                doi: 10.1002/jor.20456pubmed: 17676628google scholar: lookup
              10. Wang QW, Chen ZL, Piao YJ. Mesenchymal stem cells differentiate into tenocytes by bone morphogenetic protein (BMP) 12 gene transfer.. J Biosci Bioeng 2005 Oct;100(4):418-22.
                doi: 10.1263/jbb.100.418pubmed: 16310731google scholar: lookup
              11. Barbero A, Ploegert S, Heberer M, Martin I. Plasticity of clonal populations of dedifferentiated adult human articular chondrocytes.. Arthritis Rheum 2003 May;48(5):1315-25.
                doi: 10.1002/art.10950pubmed: 12746904google scholar: lookup
              12. Riley GP. Gene expression and matrix turnover in overused and damaged tendons.. Scand J Med Sci Sports 2005 Aug;15(4):241-51.
                doi: 10.1111/j.1600-0838.2005.00456.xpubmed: 15998341google scholar: lookup
              13. Clegg PD, Strassburg S, Smith RK. Cell phenotypic variation in normal and damaged tendons.. Int J Exp Pathol 2007 Aug;88(4):227-35.
                doi: 10.1111/j.1365-2613.2007.00549.xpmc: PMC2517321pubmed: 17696903google scholar: lookup
              14. Dahlgren LA, Brower-Toland BD, Nixon AJ. Cloning and expression of type III collagen in normal and injured tendons of horses.. Am J Vet Res 2005 Feb;66(2):266-70.
                doi: 10.2460/ajvr.2005.66.266pubmed: 15757126google scholar: lookup
              15. Eriksen HA, Pajala A, Leppilahti J, Risteli J. Increased content of type III collagen at the rupture site of human Achilles tendon.. J Orthop Res 2002 Nov;20(6):1352-7.
                doi: 10.1016/S0736-0266(02)00064-5pubmed: 12472252google scholar: lookup
              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 Apr;24(4):842-55.
                doi: 10.1002/jor.20093pubmed: 16514666google scholar: lookup
              17. Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair.. J Bone Joint Surg Am 2005 Jan;87(1):187-202.
                doi: 10.2106/JBJS.D.01850pubmed: 15634833google scholar: lookup
              18. Riley GP, Harrall RL, Cawston TE, Hazleman BL, Mackie EJ. Tenascin-C and human tendon degeneration.. Am J Pathol 1996 Sep;149(3):933-43.
                pmc: PMC1865170pubmed: 8780397
              19. Ezura Y, Chakravarti S, Oldberg A, Chervoneva I, Birk DE. Differential expression of lumican and fibromodulin regulate collagen fibrillogenesis in developing mouse tendons.. J Cell Biol 2000 Nov 13;151(4):779-88.
                doi: 10.1083/jcb.151.4.779pmc: PMC2169450pubmed: 11076963google scholar: lookup
              20. Smith RK, Zunino L, Webbon PM, Heinegård D. The distribution of cartilage oligomeric matrix protein (COMP) in tendon and its variation with tendon site, age and load.. Matrix Biol 1997 Nov;16(5):255-71.
                doi: 10.1016/S0945-053X(97)90014-7pubmed: 9501326google scholar: lookup
              21. Chiquet-Ehrismann R, Tucker RP. Connective tissues: signalling by tenascins.. Int J Biochem Cell Biol 2004 Jun;36(6):1085-9.
                doi: 10.1016/j.biocel.2004.01.007pubmed: 15094123google scholar: lookup
              22. Halász K, Kassner A, Mörgelin M, Heinegård D. COMP acts as a catalyst in collagen fibrillogenesis.. J Biol Chem 2007 Oct 26;282(43):31166-73.
                doi: 10.1074/jbc.M705735200pubmed: 17716974google scholar: lookup
              23. Docheva D, Hunziker EB, Fässler R, Brandau O. Tenomodulin is necessary for tenocyte proliferation and tendon maturation.. Mol Cell Biol 2005 Jan;25(2):699-705.
                doi: 10.1128/MCB.25.2.699-705.2005pmc: PMC543433pubmed: 15632070google scholar: lookup
              24. Shukunami C, Takimoto A, Oro M, Hiraki Y. Scleraxis positively regulates the expression of tenomodulin, a differentiation marker of tenocytes.. Dev Biol 2006 Oct 1;298(1):234-47.
                doi: 10.1016/j.ydbio.2006.06.036pubmed: 16876153google scholar: lookup
              25. Zhang G, Ezura Y, Chervoneva I, Robinson PS, Beason DP, Carine ET, Soslowsky LJ, Iozzo RV, Birk DE. Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development.. J Cell Biochem 2006 Aug 15;98(6):1436-49.
                doi: 10.1002/jcb.20776pubmed: 16518859google scholar: lookup
              26. Murchison ND, Price BA, Conner DA, Keene DR, Olson EN, Tabin CJ, Schweitzer R. Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons.. Development 2007 Jul;134(14):2697-708.
                pubmed: 17567668doi: 10.1242/dev.001933google scholar: lookup
              27. Schweitzer R, Chyung JH, Murtaugh LC, Brent AE, Rosen V, Olson EN, Lassar A, Tabin CJ. Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments.. Development 2001 Oct;128(19):3855-66.
                pubmed: 11585810doi: 10.1242/dev.128.19.3855google scholar: lookup
              28. Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF. Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.. Nat Med 2007 Oct;13(10):1219-27.
                pubmed: 17828274doi: 10.1038/nm1630google scholar: lookup
              29. Ninomiya K, Miyamoto T, Imai J, Fujita N, Suzuki T, Iwasaki R, Yagi M, Watanabe S, Toyama Y, Suda T. Osteoclastic activity induces osteomodulin expression in osteoblasts.. Biochem Biophys Res Commun 2007 Oct 19;362(2):460-6.
                doi: 10.1016/j.bbrc.2007.07.193pubmed: 17714690google scholar: lookup
              30. Garvin J, Qi J, Maloney M, Banes AJ. Novel system for engineering bioartificial tendons and application of mechanical load.. Tissue Eng 2003 Oct;9(5):967-79.
                doi: 10.1089/107632703322495619pubmed: 14633381google scholar: lookup
              31. Reno C, Marchuk L, Sciore P, Frank CB, Hart DA. Rapid isolation of total RNA from small samples of hypocellular, dense connective tissues.. Biotechniques 1997 Jun;22(6):1082-6.
                pubmed: 9187757doi: 10.2144/97226bm16google scholar: lookup
              32. Clements DN, Vaughan-Thomas A, Peansukmanee S, Carter SD, Innes JF, Ollier WE, Clegg PD. Assessment of the use of RNA quality metrics for the screening of articular cartilage specimens from clinically normal dogs and dogs with osteoarthritis.. Am J Vet Res 2006 Aug;67(8):1438-44.
                doi: 10.2460/ajvr.67.8.1438pubmed: 16881859google scholar: lookup
              33. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes.. Genome Biol 2002 Jun 18;3(7):RESEARCH0034.
                doi: 10.1186/gb-2002-3-7-research0034pmc: PMC126239pubmed: 12184808google scholar: lookup
              34. Andersen CL, Jensen JL, Ørntoft TF. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets.. Cancer Res 2004 Aug 1;64(15):5245-50.
                doi: 10.1158/0008-5472.CAN-04-0496pubmed: 15289330google scholar: lookup
              35. de Palma L, Marinelli M, Memè L, Pavan M. Immunohistochemistry of the enthesis organ of the human Achilles tendon.. Foot Ankle Int 2004 Jun;25(6):414-8.
                pubmed: 15215027doi: 10.1177/107110070402500609google scholar: lookup
              36. Mehr D, Pardubsky PD, Martin JA, Buckwalter JA. Tenascin-C in tendon regions subjected to compression.. J Orthop Res 2000 Jul;18(4):537-45.
                doi: 10.1002/jor.1100180405pubmed: 11052489google scholar: lookup
              37. Vogel KG, Keller EJ, Lenhoff RJ, Campbell K, Koob TJ. Proteoglycan synthesis by fibroblast cultures initiated from regions of adult bovine tendon subjected to different mechanical forces.. Eur J Cell Biol 1986 Jun;41(1):102-12.
                pubmed: 3792332
              38. Järvinen TA, Kannus P, Järvinen TL, Jozsa L, Kalimo H, Järvinen M. Tenascin-C in the pathobiology and healing process of musculoskeletal tissue injury.. Scand J Med Sci Sports 2000 Dec;10(6):376-82.
                doi: 10.1034/j.1600-0838.2000.010006376.xpubmed: 11085568google scholar: lookup
              39. Asou Y, Nifuji A, Tsuji K, Shinomiya K, Olson EN, Koopman P, Noda M. Coordinated expression of scleraxis and Sox9 genes during embryonic development of tendons and cartilage.. J Orthop Res 2002 Jul;20(4):827-33.
                doi: 10.1016/S0736-0266(01)00169-3pubmed: 12168674google scholar: lookup
              40. Aslan H, Kimelman-Bleich N, Pelled G, Gazit D. Molecular targets for tendon neoformation.. J Clin Invest 2008 Feb;118(2):439-44.
                doi: 10.1172/JCI33944pmc: PMC2214706pubmed: 18246194google scholar: lookup
              41. de Mos M, van El B, DeGroot J, Jahr H, van Schie HT, van Arkel ER, Tol H, Heijboer R, van Osch GJ, Verhaar JA. Achilles tendinosis: changes in biochemical composition and collagen turnover rate.. Am J Sports Med 2007 Sep;35(9):1549-56.
                doi: 10.1177/0363546507301885pubmed: 17478653google scholar: lookup
              42. Alfredson H, Lorentzon M, Bäckman S, Bäckman A, Lerner UH. cDNA-arrays and real-time quantitative PCR techniques in the investigation of chronic Achilles tendinosis.. J Orthop Res 2003 Nov;21(6):970-5.
                doi: 10.1016/S0736-0266(03)00107-4pubmed: 14554207google scholar: lookup
              43. Ireland D, Harrall R, Curry V, Holloway G, Hackney R, Hazleman B, Riley G. Multiple changes in gene expression in chronic human Achilles tendinopathy.. Matrix Biol 2001 Jun;20(3):159-69.
                doi: 10.1016/S0945-053X(01)00128-7pubmed: 11420148google scholar: lookup
              44. Sawaguchi N, Majima T, Iwasaki N, Funakoshi T, Shimode K, Onodera T, Minami A. Extracellular matrix modulates expression of cell-surface proteoglycan genes in fibroblasts.. Connect Tissue Res 2006;47(3):141-8.
                doi: 10.1080/03008200600685459pubmed: 16753807google scholar: lookup
              45. Yao L, Bestwick CS, Bestwick LA, Maffulli N, Aspden RM. Phenotypic drift in human tenocyte culture.. Tissue Eng 2006 Jul;12(7):1843-9.
                doi: 10.1089/ten.2006.12.1843pubmed: 16889514google scholar: lookup
              46. Zhang L, Tran N, Chen HQ, Kahn CJ, Marchal S, Groubatch F, Wang X. Time-related changes in expression of collagen types I and III and of tenascin-C in rat bone mesenchymal stem cells under co-culture with ligament fibroblasts or uniaxial stretching.. Cell Tissue Res 2008 Apr;332(1):101-9.
                doi: 10.1007/s00441-007-0564-6pubmed: 18196274google scholar: lookup
              47. Kapacee Z, Richardson SH, Lu Y, Starborg T, Holmes DF, Baar K, Kadler KE. Tension is required for fibripositor formation.. Matrix Biol 2008 May;27(4):371-5.
                doi: 10.1016/j.matbio.2007.11.006pubmed: 18262777google scholar: lookup
              48. Maccoux LJ, Clements DN, Salway F, Day PJ. Identification of new reference genes for the normalisation of canine osteoarthritic joint tissue transcripts from microarray data.. BMC Mol Biol 2007 Jul 25;8:62.
                doi: 10.1186/1471-2199-8-62pmc: PMC1976117pubmed: 17651481google scholar: lookup

              Citations

              This article has been cited 49 times.
              1. Ploeg MC, Munts C, Seddiqi T, Ten Brink TJL, Breemhaar J, Moroni L, Prinzen FW, van Nieuwenhoven FA. Culturing of Cardiac Fibroblasts in Engineered Heart Matrix Reduces Myofibroblast Differentiation but Maintains Their Response to Cyclic Stretch and Transforming Growth Factor β1. Bioengineering (Basel) 2022 Oct 14;9(10).
                doi: 10.3390/bioengineering9100551pubmed: 36290519google scholar: lookup
              2. Shojaee A, Ejeian F, Parham A, Nasr Esfahani MH. Optimizing Tenogenic Differentiation of Equine Adipose-Derived Mesenchymal Stem Cells (eq-ASC) Using TGFB3 Along with BMP Antagonists. Cell J 2022 Jul 27;24(7):370-379.
                doi: 10.22074/cellj.2022.7892pubmed: 36043405google scholar: lookup
              3. Konar S, Bolam SM, Coleman B, Dalbeth N, McGlashan SR, Leung S, Cornish J, Naot D, Musson DS. Changes in Physiological Tendon Substrate Stiffness Have Moderate Effects on Tendon-Derived Cell Growth and Immune Cell Activation. Front Bioeng Biotechnol 2022;10:800748.
                doi: 10.3389/fbioe.2022.800748pubmed: 35295642google scholar: lookup
              4. Colbath G, Murray A, Siatkowski S, Pate T, Krussig M, Pill S, Hawkins R, Tokish J, Mercuri J. Autograft Long Head Biceps Tendon Can Be Used as a Scaffold for Biologically Augmenting Rotator Cuff Repairs. Arthroscopy 2022 Jan;38(1):38-48.
                doi: 10.1016/j.arthro.2021.05.064pubmed: 34126215google scholar: lookup
              5. Laurent A, Abdel-Sayed P, Grognuz A, Scaletta C, Hirt-Burri N, Michetti M, de Buys Roessingh AS, Raffoul W, Kronen P, Nuss K, von Rechenberg B, Applegate LA, Darwiche SE. Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation. Biomedicines 2021 Apr 3;9(4).
                doi: 10.3390/biomedicines9040380pubmed: 33916829google scholar: lookup
              6. Yang F, Richardson DW. Comparative Analysis of Tenogenic Gene Expression in Tenocyte-Derived Induced Pluripotent Stem Cells and Bone Marrow-Derived Mesenchymal Stem Cells in Response to Biochemical and Biomechanical Stimuli. Stem Cells Int 2021;2021:8835576.
                doi: 10.1155/2021/8835576pubmed: 33510795google scholar: lookup
              7. Laurent A, Hirt-Burri N, Scaletta C, Michetti M, de Buys Roessingh AS, Raffoul W, Applegate LA. Holistic Approach of Swiss Fetal Progenitor Cell Banking: Optimizing Safe and Sustainable Substrates for Regenerative Medicine and Biotechnology. Front Bioeng Biotechnol 2020;8:557758.
                doi: 10.3389/fbioe.2020.557758pubmed: 33195124google scholar: lookup
              8. Zamboulis DE, Thorpe CT, Ashraf Kharaz Y, Birch HL, Screen HR, Clegg PD. Postnatal mechanical loading drives adaptation of tissues primarily through modulation of the non-collagenous matrix. Elife 2020 Oct 16;9.
                doi: 10.7554/eLife.58075pubmed: 33063662google scholar: lookup
              9. Paterson YZ, Cribbs A, Espenel M, Smith EJ, Henson FMD, Guest DJ. Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes. Stem Cell Res Ther 2020 May 19;11(1):184.
                doi: 10.1186/s13287-020-01692-wpubmed: 32430075google scholar: lookup
              10. Jackson JE, Kopecki Z, Anderson PJ, Cowin AJ. In vitro analysis of the effect of Flightless I on murine tenocyte cellular functions. J Orthop Surg Res 2020 May 12;15(1):170.
                doi: 10.1186/s13018-020-01692-9pubmed: 32398080google scholar: lookup
              11. Ribitsch I, Gueltekin S, Keith MF, Minichmair K, Peham C, Jenner F, Egerbacher M. Age-related changes of tendon fibril micro-morphology and gene expression. J Anat 2020 Apr;236(4):688-700.
                doi: 10.1111/joa.13125pubmed: 31792963google scholar: lookup
              12. Soreide E, Denbeigh JM, Lewallen EA, Thaler R, Samsonraj RM, Jones DL, Xu W, Larson D, Nordsletten L, Kakar S, van Wijnen AJ. A multi-chamber tissue culture device for load-dependent parallel evaluation of tendon explants. BMC Musculoskelet Disord 2019 Nov 18;20(1):549.
                doi: 10.1186/s12891-019-2896-2pubmed: 31739778google scholar: lookup
              13. Roth SP, Brehm W, Groß C, Scheibe P, Schubert S, Burk J. Transforming Growth Factor Beta 3-Loaded Decellularized Equine Tendon Matrix for Orthopedic Tissue Engineering. Int J Mol Sci 2019 Nov 3;20(21).
                doi: 10.3390/ijms20215474pubmed: 31684150google scholar: lookup
              14. Ragni E, Perucca Orfei C, Bowles AC, de Girolamo L, Correa D. Reliable Reference Genes for Gene Expression Assessment in Tendon-Derived Cells under Inflammatory and Pro-Fibrotic/Healing Stimuli. Cells 2019 Oct 1;8(10).
                doi: 10.3390/cells8101188pubmed: 31581587google scholar: lookup
              15. Zhu Q, Zhang Y, Tighe S, Liu Y, Zhu Y, Hu M. Human Trabecular Meshwork Progenitors. Int J Med Sci 2019;16(5):704-710.
                doi: 10.7150/ijms.32089pubmed: 31217738google scholar: lookup
              16. Jo CH, Lim HJ, Yoon KS. Characterization of Tendon-Specific Markers in Various Human Tissues, Tenocytes and Mesenchymal Stem Cells. Tissue Eng Regen Med 2019 Apr;16(2):151-159.
                doi: 10.1007/s13770-019-00182-2pubmed: 30989042google scholar: lookup
              17. Brandt L, Schubert S, Scheibe P, Brehm W, Franzen J, Gross C, Burk J. Tenogenic Properties of Mesenchymal Progenitor Cells Are Compromised in an Inflammatory Environment. Int J Mol Sci 2018 Aug 28;19(9).
                doi: 10.3390/ijms19092549pubmed: 30154348google scholar: lookup
              18. Nichols AEC, Settlage RE, Werre SR, Dahlgren LA. Novel roles for scleraxis in regulating adult tenocyte function. BMC Cell Biol 2018 Aug 7;19(1):14.
                doi: 10.1186/s12860-018-0166-zpubmed: 30086712google scholar: lookup
              19. Cassano JM, Schnabel LV, Goodale MB, Fortier LA. Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment. Stem Cell Res Ther 2018 Apr 3;9(1):82.
                doi: 10.1186/s13287-018-0840-2pubmed: 29615127google scholar: lookup
              20. Kuemmerle JM, Theiss F, Okoniewski MJ, Weber FA, Hemmi S, Mirsaidi A, Richards PJ, Cinelli P. Identification of Novel Equine (Equus caballus) Tendon Markers Using RNA Sequencing. Genes (Basel) 2016 Nov 10;7(11).
                doi: 10.3390/genes7110097pubmed: 27834918google scholar: lookup
              21. Grier WK, Iyoha EM, Harley BAC. The influence of pore size and stiffness on tenocyte bioactivity and transcriptomic stability in collagen-GAG scaffolds. J Mech Behav Biomed Mater 2017 Jan;65:295-305.
                doi: 10.1016/j.jmbbm.2016.08.034pubmed: 27614271google scholar: lookup
              22. Nogueira AC Jr, Júnior Mde J. The effects of laser treatment in tendinopathy: a systematic review. Acta Ortop Bras 2015 Jan-Feb;23(1):47-9.
                doi: 10.1590/1413-78522015230100513pubmed: 26327796google scholar: lookup
              23. Youngstrom DW, Rajpar I, Kaplan DL, Barrett JG. A bioreactor system for in vitro tendon differentiation and tendon tissue engineering. J Orthop Res 2015 Jun;33(6):911-8.
                doi: 10.1002/jor.22848pubmed: 25664422google scholar: lookup
              24. Pawelec KM, Wardale RJ, Best SM, Cameron RE. The effects of scaffold architecture and fibrin gel addition on tendon cell phenotype. J Mater Sci Mater Med 2015 Jan;26(1):5349.
                doi: 10.1007/s10856-014-5349-3pubmed: 25578703google scholar: lookup
              25. Burk J, Gittel C, Heller S, Pfeiffer B, Paebst F, Ahrberg AB, Brehm W. Gene expression of tendon markers in mesenchymal stromal cells derived from different sources. BMC Res Notes 2014 Nov 20;7:826.
                doi: 10.1186/1756-0500-7-826pubmed: 25412928google scholar: lookup
              26. Nemoto M, Kizaki K, Yamamoto Y, Oonuma T, Hashizume K. Tenascin-C Expression in Equine Tendon-derived Cells During Proliferation and Migration. J Equine Sci 2013;24(2):17-24.
                doi: 10.1294/jes.24.17pubmed: 24833997google scholar: lookup
              27. Brown JP, Finley VG, Kuo CK. Embryonic mechanical and soluble cues regulate tendon progenitor cell gene expression as a function of developmental stage and anatomical origin. J Biomech 2014 Jan 3;47(1):214-22.
                doi: 10.1016/j.jbiomech.2013.09.018pubmed: 24231248google scholar: lookup
              28. Gittel C, Brehm W, Burk J, Juelke H, Staszyk C, Ribitsch I. Isolation of equine multipotent mesenchymal stromal cells by enzymatic tissue digestion or explant technique: comparison of cellular properties. BMC Vet Res 2013 Oct 29;9:221.
                doi: 10.1186/1746-6148-9-221pubmed: 24168625google scholar: lookup
              29. Rich T, Henderson LB, Becker DL, Cornell H, Patterson-Kane JC. Indicators of replicative damage in equine tendon fibroblast monolayers. BMC Vet Res 2013 Sep 11;9:180.
                doi: 10.1186/1746-6148-9-180pubmed: 24025445google scholar: lookup
              30. Peffers M, Liu X, Clegg P. Transcriptomic signatures in cartilage ageing. Arthritis Res Ther 2013 Aug 23;15(4):R98.
                doi: 10.1186/ar4278pubmed: 23971731google scholar: lookup
              31. Carvalho Ade M, Badial PR, Álvarez LE, Yamada AL, Borges AS, Deffune E, Hussni CA, Garcia Alves AL. Equine tendonitis therapy using mesenchymal stem cells and platelet concentrates: a randomized controlled trial. Stem Cell Res Ther 2013 Jul 22;4(4):85.
                doi: 10.1186/scrt236pubmed: 23876512google scholar: lookup
              32. Hortensius RA, Harley BA. The use of bioinspired alterations in the glycosaminoglycan content of collagen-GAG scaffolds to regulate cell activity. Biomaterials 2013 Oct;34(31):7645-52.
                doi: 10.1016/j.biomaterials.2013.06.056pubmed: 23871542google scholar: lookup
              33. Bosworth LA, Alam N, Wong JK, Downes S. Investigation of 2D and 3D electrospun scaffolds intended for tendon repair. J Mater Sci Mater Med 2013 Jun;24(6):1605-14.
                doi: 10.1007/s10856-013-4911-8pubmed: 23504088google scholar: lookup
              34. Reed SA, Johnson SE. Expression of scleraxis and tenascin C in equine adipose and umbilical cord blood derived stem cells is dependent upon substrata and FGF supplementation. Cytotechnology 2014 Jan;66(1):27-35.
                doi: 10.1007/s10616-012-9533-3pubmed: 23299298google scholar: lookup
              35. Caliari SR, Harley BA. Composite growth factor supplementation strategies to enhance tenocyte bioactivity in aligned collagen-GAG scaffolds. Tissue Eng Part A 2013 May;19(9-10):1100-12.
                doi: 10.1089/ten.TEA.2012.0497pubmed: 23157454google scholar: lookup
              36. Chooi WH, Zhou R, Yeo SS, Zhang F, Wang DA. Determination and validation of reference gene stability for qPCR analysis in polysaccharide hydrogel-based 3D chondrocytes and mesenchymal stem cell cultural models. Mol Biotechnol 2013 Jun;54(2):623-33.
                doi: 10.1007/s12033-012-9604-xpubmed: 23054629google scholar: lookup
              37. Caliari SR, Weisgerber DW, Ramirez MA, Kelkhoff DO, Harley BA. The influence of collagen-glycosaminoglycan scaffold relative density and microstructural anisotropy on tenocyte bioactivity and transcriptomic stability. J Mech Behav Biomed Mater 2012 Jul;11:27-40.
                doi: 10.1016/j.jmbbm.2011.12.004pubmed: 22658152google scholar: lookup
              38. Nelson EF, Huang CW, Ewel JM, Chang AA, Yuan C. Halofuginone down-regulates Smad3 expression and inhibits the TGFbeta-induced expression of fibrotic markers in human corneal fibroblasts. Mol Vis 2012;18:479-87.
                pubmed: 22393274
              39. Riehl BD, Park JH, Kwon IK, Lim JY. Mechanical stretching for tissue engineering: two-dimensional and three-dimensional constructs. Tissue Eng Part B Rev 2012 Aug;18(4):288-300.
                doi: 10.1089/ten.TEB.2011.0465pubmed: 22335794google scholar: lookup
              40. Mazzocca AD, Chowaniec D, McCarthy MB, Beitzel K, Cote MP, McKinnon W, Arciero R. In vitro changes in human tenocyte cultures obtained from proximal biceps tendon: multiple passages result in changes in routine cell markers. Knee Surg Sports Traumatol Arthrosc 2012 Sep;20(9):1666-72.
                doi: 10.1007/s00167-011-1711-xpubmed: 22005966google scholar: lookup
              41. Enea D, Henson F, Kew S, Wardale J, Getgood A, Brooks R, Rushton N. Extruded collagen fibres for tissue engineering applications: effect of crosslinking method on mechanical and biological properties. J Mater Sci Mater Med 2011 Jun;22(6):1569-78.
                doi: 10.1007/s10856-011-4336-1pubmed: 21556975google scholar: lookup
              42. Beekman L, Tohver T, Dardari R, Léguillette R. Evaluation of suitable reference genes for gene expression studies in bronchoalveolar lavage cells from horses with inflammatory airway disease. BMC Mol Biol 2011 Jan 28;12:5.
                doi: 10.1186/1471-2199-12-5pubmed: 21272375google scholar: lookup
              43. Cui Q, Wang Z, Jiang D, Qu L, Guo J, Li Z. HGF inhibits TGF-β1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat. Eur J Appl Physiol 2011 Jul;111(7):1457-63.
                doi: 10.1007/s00421-010-1764-4pubmed: 21165643google scholar: lookup
              44. Peffers MJ, Milner PI, Tew SR, Clegg PD. Regulation of SOX9 in normal and osteoarthritic equine articular chondrocytes by hyperosmotic loading. Osteoarthritis Cartilage 2010 Nov;18(11):1502-8.
                doi: 10.1016/j.joca.2010.08.011pubmed: 20800688google scholar: lookup
              45. Marr N, Meeson R, Piercy RJ, Hildyard JCW, Thorpe CT. Evaluation of suitable reference genes for qPCR normalisation of gene expression in a Achilles tendon injury model. PLoS One 2024;19(8):e0306678.
                doi: 10.1371/journal.pone.0306678pubmed: 39190750google scholar: lookup
              46. Ferretti L, Moccia V, Centelleghe C, Venerando A, Dettin M, Sieni E, Zamuner A, Caicci F, Castagnaro M, Zappulli V, Mazzariol S. Bottlenose dolphin (Tursiops truncatus) immortalized fibroblasts on novel 3D in vitro collagen-free scaffolds. PLoS One 2024;19(6):e0304992.
                doi: 10.1371/journal.pone.0304992pubmed: 38861523google scholar: lookup
              47. DiIorio SE, Young B, Parker JB, Griffin MF, Longaker MT. Understanding Tendon Fibroblast Biology and Heterogeneity. Biomedicines 2024 Apr 12;12(4).
                doi: 10.3390/biomedicines12040859pubmed: 38672213google scholar: lookup
              48. Taguchi T, Lopez M, Takawira C. Viable tendon neotissue from adult adipose-derived multipotent stromal cells. Front Bioeng Biotechnol 2023;11:1290693.
                doi: 10.3389/fbioe.2023.1290693pubmed: 38260742google scholar: lookup
              49. Abhari RE, Snelling SJB, Augustynak E, Davis S, Fischer R, Carr AJ, Mouthuy PA. A Hybrid Electrospun-Extruded Polydioxanone Suture for Tendon Tissue Regeneration. Tissue Eng Part A 2024 Mar;30(5-6):214-224.
                doi: 10.1089/ten.TEA.2023.0273pubmed: 38126344google scholar: lookup
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