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Home / Equine Research Bank / Stem Cells Int / Comparative Analysis of Tenogenic Gene Expression in Tenocyt...
Stem cells international2021; 2021; 8835576; doi: 10.1155/2021/8835576

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.

Abstract: The tendon is highly prone to injury, overuse, or age-related degeneration in both humans and horses. Natural healing of injured tendon is poor, and cell-based therapeutic treatment is still a significant clinical challenge. In this study, we extensively investigated the expression of tenogenic genes in equine bone marrow mesenchymal stem cells (BMSCs) and tenocyte-derived induced pluripotent stem cells (teno-iPSCs) stimulated by growth factors (TGF-3 and BMP12) combined with ectopic expression of tenogenic transcription factor MKX or cyclic uniaxial mechanical stretch. Western blotting revealed that TGF-3 and BMP12 increased the expression of transcription factors SCX and MKX in both cells, but the tenocyte marker tenomodulin (TNMD) was detected only in BMSCs and upregulated by either inducer. On the other hand, quantitative real-time PCR showed that TGF-3 increased the expression of , , , and in BMSCs and , , , , and in teno-iPSCs. BMP12 treatment elevated , , , , and in teno-iPSCs. Overexpression of MKX increased , , , and in BMSCs and , , , , and in teno-iPSCs; TGF-3 further enhanced in BMSCs. Moreover, mechanical stretch increased , , , , and in BMSCs and , , , , , , and in teno-iPSCs; TGF-3 tended to further elevate , , and in BMSCs and , , , , and in teno-iPSCs, while BMP12 further uptrended the expression of and in BMSCs and in teno-iPSCs. Additionally, the aforementioned tenogenic inducers also affected the expression of signaling regulators , , and in BMSCs and teno-iPSCs. Taken together, our data demonstrate that, in respect to the tenocyte-lineage-specific gene expression, BMSCs and teno-iPSCs respond differently to the tenogenic stimuli, which may affect the outcome of their application in tendon repair or regeneration.
Copyright © 2021 Feikun Yang and Dean W. Richardson.
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Publication Date: 2021-01-13 PubMed ID: 33510795PubMed Central: PMC7825360DOI: 10.1155/2021/8835576Google Scholar: Lookup
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  • Journal Article

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 investigates how different stem cells, specifically equine bone marrow mesenchymal stem cells (BMSCs) and tenocyte-derived induced pluripotent stem cells (teno-iPSCs), respond to various biochemical and biomechanical stimuli, in order to identify their potential in aiding tendon repair and regeneration.

Introduction and Research Objective

  • The study focused on understanding the gene expression of tenogenic (relating to tendon cell development and specialization) genes in two different stem cell types: equine bone marrow mesenchymal stem cells (BMSCs) and tenocyte-derived induced pluripotent stem cells (teno-iPSCs).
  • The researchers explored how these cells respond to different stimuli, specifically growth factors (TGF-3 and BMP12), the tenogenic transcription factor MKX, and mechanical strain.
  • The aim was to identify potential cellular mechanisms that could support tendon repair and regeneration, which is currently a medical challenge due to poor natural healing ability of tendons.

Research Methodology

  • Western blotting technique was used to detect protein changes in response to the stimuli. The researchers were particularly interested in the transcription factors SCX and MKX, and the tenocyte marker tenomodulin (TNMD).
  • Quantitative real-time PCR (a technique used to measure gene expression) was used to evaluate the expression of various genes associated with tendon development and healing in the two stem cell types when subjected to the stimuli.

Research Findings

  • The results showed that TGF-3 and BMP12 increased the expression of transcription factors SCX and MKX in both BMSCs and teno-iPSCs, but the expression of tenomodulin (TNMD) was only seen in BMSCs and further increased by either trigger.
  • The expression of numerous genes was affected differently in both types of stem cells when treated with the growth factors, overexpressed MKX, or subjected to mechanical stretch.
  • Both TGF-3 and BMP12 also influenced the expression of signaling regulators within the cells.

Conclusion

  • The study concludes that BMSCs and teno-iPSCs respond differently to tenogenic stimuli based on gene expression specific to tendon cells.
  • This differential response could potentially impact their usage in tendon repair or regeneration therapies, suggesting further investigation is essential in determining optimal cell type and stimuli for tendon healing.

Cite This Article

APA
Yang F, Richardson DW. (2021). 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, 8835576. https://doi.org/10.1155/2021/8835576

Publication

Stem cells international
ISSN: 1687-966X
NlmUniqueID: 101535822
Country: United States
Language: English
Volume: 2021
Pages: 8835576
PII: 8835576

Researcher Affiliations

Yang, Feikun
  • Department of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, 382 West Street Road, Kennett Square PA 19348, USA.
Richardson, Dean W
  • Department of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, 382 West Street Road, Kennett Square PA 19348, USA.

Conflict of Interest Statement

The authors declare that they have no competing interests.

References

This article includes 85 references
  1. Nourissat G, Berenbaum F, Duprez D. Tendon injury: from biology to tendon repair.. Nat Rev Rheumatol 2015 Apr;11(4):223-33.
    doi: 10.1038/nrrheum.2015.26pubmed: 25734975google scholar: lookup
  2. Gaspar D, Spanoudes K, Holladay C, Pandit A, Zeugolis D. Progress in cell-based therapies for tendon repair.. Adv Drug Deliv Rev 2015 Apr;84:240-56.
    doi: 10.1016/j.addr.2014.11.023pubmed: 25543005google scholar: lookup
  3. 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.
    doi: 10.1038/nm1630pubmed: 17828274google scholar: lookup
  4. Tan Q, Lui PP, Rui YF, Wong YM. Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering.. Tissue Eng Part A 2012 Apr;18(7-8):840-51.
    doi: 10.1089/ten.tea.2011.0362pmc: PMC3313612pubmed: 22011320google scholar: lookup
  5. Guo J, Chan KM, Zhang JF, Li G. Tendon-derived stem cells undergo spontaneous tenogenic differentiation.. Exp Cell Res 2016 Feb 1;341(1):1-7.
    doi: 10.1016/j.yexcr.2016.01.007pubmed: 26794903google scholar: lookup
  6. Webb S, Gabrelow C, Pierce J, Gibb E, Elliott J. Retinoic acid receptor signaling preserves tendon stem cell characteristics and prevents spontaneous differentiation in vitrox.. Stem Cell Res Ther 2016 Mar 22;7:45.
    doi: 10.1186/s13287-016-0306-3pmc: PMC4802591pubmed: 27001426google scholar: lookup
  7. Harris MT, Butler DL, Boivin GP, Florer JB, Schantz EJ, Wenstrup RJ. Mesenchymal stem cells used for rabbit tendon repair can form ectopic bone and express alkaline phosphatase activity in constructs.. J Orthop Res 2004 Sep;22(5):998-1003.
    doi: 10.1016/j.orthres.2004.02.012pubmed: 15304271google scholar: lookup
  8. Xu W, Wang Y, Liu E, Sun Y, Luo Z, Xu Z, Liu W, Zhong L, Lv Y, Wang A, Tang Z, Li S, Yang L. Human iPSC-derived neural crest stem cells promote tendon repair in a rat patellar tendon window defect model.. Tissue Eng Part A 2013 Nov;19(21-22):2439-51.
    doi: 10.1089/ten.tea.2012.0453pmc: PMC3807699pubmed: 23815150google scholar: lookup
  9. Komura S, Satake T, Goto A, Aoki H, Shibata H, Ito K, Hirakawa A, Yamada Y, Akiyama H. Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice.. Sci Rep 2020 Mar 4;10(1):3992.
    doi: 10.1038/s41598-020-61063-6pmc: PMC7055210pubmed: 32132649google scholar: lookup
  10. Woods S, Bates N, Dunn SL, Serracino-Inglott F, Hardingham TE, Kimber SJ. Generation of Human-Induced Pluripotent Stem Cells From Anterior Cruciate Ligament.. J Orthop Res 2020 Jan;38(1):92-104.
    pmc: PMC6972590pubmed: 31613026doi: 10.1002/jor.24493google scholar: lookup
  11. Gorecka J, Kostiuk V, Fereydooni A, Gonzalez L, Luo J, Dash B, Isaji T, Ono S, Liu S, Lee SR, Xu J, Liu J, Taniguchi R, Yastula B, Hsia HC, Qyang Y, Dardik A. The potential and limitations of induced pluripotent stem cells to achieve wound healing.. Stem Cell Res Ther 2019 Mar 12;10(1):87.
    doi: 10.1186/s13287-019-1185-1pmc: PMC6416973pubmed: 30867069google scholar: lookup
  12. Wolfman NM, Hattersley G, Cox K, Celeste AJ, Nelson R, Yamaji N, Dube JL, DiBlasio-Smith E, Nove J, Song JJ, Wozney JM, Rosen V. Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family.. J Clin Invest 1997 Jul 15;100(2):321-30.
    doi: 10.1172/JCI119537pmc: PMC508194pubmed: 9218508google scholar: lookup
  13. Pryce BA, Watson SS, Murchison ND, Staverosky JA, Dünker N, Schweitzer R. Recruitment and maintenance of tendon progenitors by TGFbeta signaling are essential for tendon formation.. Development 2009 Apr;136(8):1351-61.
    doi: 10.1242/dev.027342pmc: PMC2687466pubmed: 19304887google scholar: lookup
  14. Barsby T, Guest D. Transforming growth factor beta3 promotes tendon differentiation of equine embryo-derived stem cells.. Tissue Eng Part A 2013 Oct;19(19-20):2156-65.
    doi: 10.1089/ten.tea.2012.0372pubmed: 23611525google scholar: lookup
  15. Tan GK, Pryce BA, Stabio A, Brigande JV, Wang C, Xia Z, Tufa SF, Keene DR, Schweitzer R. Tgfβ signaling is critical for maintenance of the tendon cell fate.. Elife 2020 Jan 21;9.
    doi: 10.7554/elife.52695pmc: PMC7025861pubmed: 31961320google scholar: lookup
  16. Chan KM, Fu SC, Wong YP, Hui WC, Cheuk YC, Wong MW. Expression of transforming growth factor beta isoforms and their roles in tendon healing.. Wound Repair Regen 2008 May-Jun;16(3):399-407.
    doi: 10.1111/j.1524-475X.2008.00379.xpubmed: 18471258google scholar: lookup
  17. Kapacee Z, Yeung CY, Lu Y, Crabtree D, Holmes DF, Kadler KE. Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3.. Matrix Biol 2010 Oct;29(8):668-77.
    doi: 10.1016/j.matbio.2010.08.005pmc: PMC3611595pubmed: 20736064google scholar: lookup
  18. Bavin EP, Smith O, Baird AE, Smith LC, Guest DJ. Equine Induced Pluripotent Stem Cells have a Reduced Tendon Differentiation Capacity Compared to Embryonic Stem Cells.. Front Vet Sci 2015;2:55.
    doi: 10.3389/fvets.2015.00055pmc: PMC4672282pubmed: 26664982google scholar: lookup
  19. Mikic B, Schalet BJ, Clark RT, Gaschen V, Hunziker EB. GDF-5 deficiency in mice alters the ultrastructure, mechanical properties and composition of the Achilles tendon.. J Orthop Res 2001 May;19(3):365-71.
    doi: 10.1016/S0736-0266(00)90018-4pubmed: 11398847google scholar: lookup
  20. Mikic B, Rossmeier K, Bierwert L. Sexual dimorphism in the effect of GDF-6 deficiency on murine tendon.. J Orthop Res 2009 Dec;27(12):1603-11.
    doi: 10.1002/jor.20916pmc: PMC2925107pubmed: 19492402google scholar: lookup
  21. Mikic B, Bierwert L, Tsou D. Achilles tendon characterization in GDF-7 deficient mice.. J Orthop Res 2006 Apr;24(4):831-41.
    doi: 10.1002/jor.20092pubmed: 16514625google scholar: lookup
  22. Violini S, Ramelli P, Pisani LF, Gorni C, Mariani P. Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12.. BMC Cell Biol 2009 Apr 22;10:29.
    doi: 10.1186/1471-2121-10-29pmc: PMC2678092pubmed: 19383177google scholar: lookup
  23. Gulati BR, Kumar R, Mohanty N, Kumar P, Somasundaram RK, Yadav PS. Bone morphogenetic protein-12 induces tenogenic differentiation of mesenchymal stem cells derived from equine amniotic fluid.. Cells Tissues Organs 2013;198(5):377-89.
    doi: 10.1159/000358231pubmed: 24662023google scholar: lookup
  24. Shen H, Gelberman RH, Silva MJ, Sakiyama-Elbert SE, Thomopoulos S. BMP12 induces tenogenic differentiation of adipose-derived stromal cells.. PLoS One 2013;8(10):e77613.
    doi: 10.1371/journal.pone.0077613pmc: PMC3796462pubmed: 24155967google scholar: lookup
  25. Zarychta-Wiśniewska W, Burdzinska A, Kulesza A, Gala K, Kaleta B, Zielniok K, Siennicka K, Sabat M, Paczek L. Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties.. BMC Cell Biol 2017 Feb 18;18(1):13.
    doi: 10.1186/s12860-017-0129-9pmc: PMC5316159pubmed: 28214472google scholar: lookup
  26. Chen X, Yin Z, Chen JL, Liu HH, Shen WL, Fang Z, Zhu T, Ji J, Ouyang HW, Zou XH. Scleraxis-overexpressed human embryonic stem cell-derived mesenchymal stem cells for tendon tissue engineering with knitted silk-collagen scaffold.. Tissue Eng Part A 2014 Jun;20(11-12):1583-92.
    doi: 10.1089/ten.tea.2012.0656pubmed: 24328506google scholar: lookup
  27. Otabe K, Nakahara H, Hasegawa A, Matsukawa T, Ayabe F, Onizuka N, Inui M, Takada S, Ito Y, Sekiya I, Muneta T, Lotz M, Asahara H. Transcription factor Mohawk controls tenogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo.. J Orthop Res 2015 Jan;33(1):1-8.
    doi: 10.1002/jor.22750pmc: PMC4294629pubmed: 25312837google scholar: lookup
  28. Yang F, Zhang A, Richardson DW. Regulation of the tenogenic gene expression in equine tenocyte-derived induced pluripotent stem cells by mechanical loading and Mohawk.. Stem Cell Res 2019 Aug;39:101489.
    doi: 10.1016/j.scr.2019.101489pmc: PMC7082636pubmed: 31277043google scholar: lookup
  29. Gaut L, Robert N, Delalande A, Bonnin MA, Pichon C, Duprez D. EGR1 Regulates Transcription Downstream of Mechanical Signals during Tendon Formation and Healing.. PLoS One 2016;11(11):e0166237.
    doi: 10.1371/journal.pone.0166237pmc: PMC5098749pubmed: 27820865google scholar: lookup
  30. Yin Z, Guo J, Wu TY, Chen X, Xu LL, Lin SE, Sun YX, Chan KM, Ouyang H, Li G. Stepwise Differentiation of Mesenchymal Stem Cells Augments Tendon-Like Tissue Formation and Defect Repair In Vivo.. Stem Cells Transl Med 2016 Aug;5(8):1106-16.
    doi: 10.5966/sctm.2015-0215pmc: PMC4954446pubmed: 27280798google scholar: lookup
  31. Vander Ark A, Cao J, Li X. TGF-β receptors: In and beyond TGF-β signaling.. Cell Signal 2018 Dec;52:112-120.
    doi: 10.1016/j.cellsig.2018.09.002pubmed: 30184463google scholar: lookup
  32. Zhang YE. Non-Smad Signaling Pathways of the TGF-β Family.. Cold Spring Harb Perspect Biol 2017 Feb 1;9(2).
    doi: 10.1101/cshperspect.a022129pmc: PMC5287080pubmed: 27864313google scholar: lookup
  33. Nakao A, Afrakhte M, Morén A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH, ten Dijke P. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling.. Nature 1997 Oct 9;389(6651):631-5.
    doi: 10.1038/39369pubmed: 9335507google scholar: lookup
  34. Havis E, Bonnin MA, Esteves de Lima J, Charvet B, Milet C, Duprez D. TGFβ and FGF promote tendon progenitor fate and act downstream of muscle contraction to regulate tendon differentiation during chick limb development.. Development 2016 Oct 15;143(20):3839-3851.
    doi: 10.1242/dev.136242pubmed: 27624906google scholar: lookup
  35. 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.
    doi: 10.1242/dev.001933pubmed: 17567668google scholar: lookup
  36. Liu W, Watson SS, Lan Y, Keene DR, Ovitt CE, Liu H, Schweitzer R, Jiang R. The atypical homeodomain transcription factor Mohawk controls tendon morphogenesis.. Mol Cell Biol 2010 Oct;30(20):4797-807.
    doi: 10.1128/MCB.00207-10pmc: PMC2950547pubmed: 20696843google scholar: lookup
  37. Suzuki H, Ito Y, Shinohara M, Yamashita S, Ichinose S, Kishida A, Oyaizu T, Kayama T, Nakamichi R, Koda N, Yagishita K, Lotz MK, Okawa A, Asahara H. Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis.. Proc Natl Acad Sci U S A 2016 Jul 12;113(28):7840-5.
    doi: 10.1073/pnas.1522054113pmc: PMC4948356pubmed: 27370800google scholar: lookup
  38. Guerquin MJ, Charvet B, Nourissat G, Havis E, Ronsin O, Bonnin MA, Ruggiu M, Olivera-Martinez I, Robert N, Lu Y, Kadler KE, Baumberger T, Doursounian L, Berenbaum F, Duprez D. Transcription factor EGR1 directs tendon differentiation and promotes tendon repair.. J Clin Invest 2013 Aug;123(8):3564-76.
    doi: 10.1172/JCI67521pmc: PMC4011025pubmed: 23863709google scholar: lookup
  39. Safi HA, Nagalingam RS, Czubryt MP. Scleraxis: a force-responsive cell phenotype regulator. Current Opinion in Physiology 2018;1:104–110.
    doi: 10.1016/j.cophys.2017.07.004google scholar: lookup
  40. 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.2013.09.018pmc: PMC4157071pubmed: 24231248google scholar: lookup
  41. Maeda T, Sakabe T, Sunaga A, Sakai K, Rivera AL, Keene DR, Sasaki T, Stavnezer E, Iannotti J, Schweitzer R, Ilic D, Baskaran H, Sakai T. Conversion of mechanical force into TGF-β-mediated biochemical signals.. Curr Biol 2011 Jun 7;21(11):933-41.
    doi: 10.1016/j.cub.2011.04.007pmc: PMC3118584pubmed: 21600772google scholar: lookup
  42. Liu H, Zhang C, Zhu S, Lu P, Zhu T, Gong X, Zhang Z, Hu J, Yin Z, Heng BC, Chen X, Ouyang HW. Mohawk promotes the tenogenesis of mesenchymal stem cells through activation of the TGFβ signaling pathway.. Stem Cells 2015 Feb;33(2):443-55.
    doi: 10.1002/stem.1866pubmed: 25332192google scholar: lookup
  43. Koda N, Sato T, Shinohara M, Ichinose S, Ito Y, Nakamichi R, Kayama T, Kataoka K, Suzuki H, Moriyama K, Asahara H. The transcription factor mohawk homeobox regulates homeostasis of the periodontal ligament.. Development 2017 Jan 15;144(2):313-320.
    doi: 10.1242/dev.135798pmc: PMC5394762pubmed: 27993989google scholar: lookup
  44. Ito Y, Toriuchi N, Yoshitaka T, Ueno-Kudoh H, Sato T, Yokoyama S, Nishida K, Akimoto T, Takahashi M, Miyaki S, Asahara H. The Mohawk homeobox gene is a critical regulator of tendon differentiation.. Proc Natl Acad Sci U S A 2010 Jun 8;107(23):10538-42.
    doi: 10.1073/pnas.1000525107pmc: PMC2890854pubmed: 20498044google scholar: lookup
  45. Kayama T, Mori M, Ito Y, Matsushima T, Nakamichi R, Suzuki H, Ichinose S, Saito M, Marumo K, Asahara H. Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon.. Mol Cell Biol 2016 Apr;36(8):1297-309.
    doi: 10.1128/MCB.00950-15pmc: PMC4836271pubmed: 26884464google scholar: lookup
  46. Lee JY, Zhou Z, Taub PJ, Ramcharan M, Li Y, Akinbiyi T, Maharam ER, Leong DJ, Laudier DM, Ruike T, Torina PJ, Zaidi M, Majeska RJ, Schaffler MB, Flatow EL, Sun HB. BMP-12 treatment of adult mesenchymal stem cells in vitro augments tendon-like tissue formation and defect repair in vivo.. PLoS One 2011 Mar 11;6(3):e17531.
    doi: 10.1371/journal.pone.0017531pmc: PMC3055887pubmed: 21412429google scholar: lookup
  47. 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
  48. Lejard V, Blais F, Guerquin MJ, Bonnet A, Bonnin MA, Havis E, Malbouyres M, Bidaud CB, Maro G, Gilardi-Hebenstreit P, Rossert J, Ruggiero F, Duprez D. EGR1 and EGR2 involvement in vertebrate tendon differentiation.. J Biol Chem 2011 Feb 18;286(7):5855-67.
    doi: 10.1074/jbc.M110.153106pmc: PMC3037698pubmed: 21173153google scholar: lookup
  49. Liu Q, Zhu Y, Qi J, Amadio PC, Moran SL, Gingery A, Zhao C. Isolation and characterization of turkey bone marrow-derived mesenchymal stem cells.. J Orthop Res 2019 Jun;37(6):1419-1428.
    doi: 10.1002/jor.24203pubmed: 30548886google scholar: lookup
  50. Fahy N, Alini M, Stoddart MJ. Mechanical stimulation of mesenchymal stem cells: Implications for cartilage tissue engineering.. J Orthop Res 2018 Jan;36(1):52-63.
    doi: 10.1002/jor.23670pubmed: 28763118google scholar: lookup
  51. Screen HR, Berk DE, Kadler KE, Ramirez F, Young MF. Tendon functional extracellular matrix.. J Orthop Res 2015 Jun;33(6):793-9.
    doi: 10.1002/jor.22818pmc: PMC4507431pubmed: 25640030google scholar: lookup
  52. Ramirez F, Tanaka S, Bou-Gharios G. Transcriptional regulation of the human alpha2(I) collagen gene (COL1A2), an informative model system to study fibrotic diseases.. Matrix Biol 2006 Aug;25(6):365-72.
    doi: 10.1016/j.matbio.2006.05.002pubmed: 16815696google scholar: lookup
  53. Thorpe CT, Birch HL, Clegg PD, Screen HR. The role of the non-collagenous matrix in tendon function.. Int J Exp Pathol 2013 Aug;94(4):248-59.
    doi: 10.1111/iep.12027pmc: PMC3721456pubmed: 23718692google scholar: lookup
  54. Zhang W, Ge Y, Cheng Q, Zhang Q, Fang L, Zheng J. Decorin is a pivotal effector in the extracellular matrix and tumour microenvironment.. Oncotarget 2018 Jan 12;9(4):5480-5491.
    doi: 10.18632/oncotarget.23869pmc: PMC5797066pubmed: 29435195google scholar: lookup
  55. Youngstrom DW, LaDow JE, Barrett JG. Tenogenesis of bone marrow-, adipose-, and tendon-derived stem cells in a dynamic bioreactor.. Connect Tissue Res 2016 Nov;57(6):454-465.
    doi: 10.3109/03008207.2015.1117458pubmed: 27028488google scholar: lookup
  56. Lohberger B, Kaltenegger H, Stuendl N, Rinner B, Leithner A, Sadoghi P. Impact of cyclic mechanical stimulation on the expression of extracellular matrix proteins in human primary rotator cuff fibroblasts.. Knee Surg Sports Traumatol Arthrosc 2016 Dec;24(12):3884-3891.
    doi: 10.1007/s00167-015-3790-6pubmed: 26392342google scholar: lookup
  57. Nichols AEC, Werre SR, Dahlgren LA. Transient Scleraxis Overexpression Combined with Cyclic Strain Enhances Ligament Cell Differentiation.. Tissue Eng Part A 2018 Oct;24(19-20):1444-1455.
    doi: 10.1089/ten.tea.2017.0481pmc: PMC6198763pubmed: 29644940google scholar: lookup
  58. Xu SY, Liu SY, Xu L, Deng SY, He YB, Li SF, Ni GX. Response of decorin to different intensity treadmill running.. Mol Med Rep 2018 Jun;17(6):7911-7917.
    doi: 10.3892/mmr.2018.8802pubmed: 29620182google scholar: lookup
  59. Svensson L, Aszódi A, Reinholt FP, Fässler R, Heinegård D, Oldberg A. Fibromodulin-null mice have abnormal collagen fibrils, tissue organization, and altered lumican deposition in tendon.. J Biol Chem 1999 Apr 2;274(14):9636-47.
    doi: 10.1074/jbc.274.14.9636pubmed: 10092650google scholar: lookup
  60. Xu Y, Wang Q, Li Y, Gan Y, Li P, Li S, Zhou Y, Zhou Q. Cyclic Tensile Strain Induces Tenogenic Differentiation of Tendon-Derived Stem Cells in Bioreactor Culture.. Biomed Res Int 2015;2015:790804.
    doi: 10.1155/2015/790804pmc: PMC4502284pubmed: 26229962google scholar: lookup
  61. Grant TM, Thompson MS, Urban J, Yu J. Elastic fibres are broadly distributed in tendon and highly localized around tenocytes.. J Anat 2013 Jun;222(6):573-9.
    doi: 10.1111/joa.12048pmc: PMC3666236pubmed: 23587025google scholar: lookup
  62. Wu YT, Su WR, Wu PT, Shen PC, Jou IM. Degradation of elastic fiber and elevated elastase expression in long head of biceps tendinopathy.. J Orthop Res 2017 Sep;35(9):1919-1926.
    doi: 10.1002/jor.23500pubmed: 27935111google scholar: lookup
  63. Thakkar D, Grant TM, Hakimi O, Carr AJ. Distribution and expression of type VI collagen and elastic fibers in human rotator cuff tendon tears.. Connect Tissue Res 2014 Oct-Dec;55(5-6):397-402.
    doi: 10.3109/03008207.2014.959119pubmed: 25166893google scholar: lookup
  64. Min J, Li B, Liu C, Guo W, Hong S, Tang J, Hong L. Extracellular matrix metabolism disorder induced by mechanical strain on human parametrial ligament fibroblasts.. Mol Med Rep 2017 May;15(5):3278-3284.
    doi: 10.3892/mmr.2017.6372pubmed: 28339064google scholar: lookup
  65. Mackie EJ, Ramsey S. Expression of tenascin in joint-associated tissues during development and postnatal growth.. J Anat 1996 Feb;188 ( Pt 1)(Pt 1):157-65.
    pmc: PMC1167643pubmed: 8655402
  66. Taylor SE, Vaughan-Thomas A, Clements DN, Pinchbeck G, Macrory LC, Smith RK, Clegg PD. Gene expression markers of tendon fibroblasts in normal and diseased tissue compared to monolayer and three dimensional culture systems.. BMC Musculoskelet Disord 2009 Feb 26;10:27.
    doi: 10.1186/1471-2474-10-27pmc: PMC2651848pubmed: 19245707google scholar: lookup
  67. Järvinen TA, Józsa L, Kannus P, Järvinen TL, Hurme T, Kvist M, Pelto-Huikko M, Kalimo H, Järvinen M. Mechanical loading regulates the expression of tenascin-C in the myotendinous junction and tendon but does not induce de novo synthesis in the skeletal muscle.. J Cell Sci 2003 Mar 1;116(Pt 5):857-66.
    doi: 10.1242/jcs.00303pubmed: 12571283google scholar: lookup
  68. Qiu Y, Lei J, Koob TJ, Temenoff JS. Cyclic tension promotes fibroblastic differentiation of human MSCs cultured on collagen-fibre scaffolds.. J Tissue Eng Regen Med 2016 Dec;10(12):989-999.
    doi: 10.1002/term.1880pubmed: 24515660google scholar: lookup
  69. 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/ijms20215474pmc: PMC6862173pubmed: 31684150google scholar: lookup
  70. Shukunami C, Takimoto A, Nishizaki Y, Yoshimoto Y, Tanaka S, Miura S, Watanabe H, Sakuma T, Yamamoto T, Kondoh G, Hiraki Y. Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes.. Sci Rep 2018 Feb 16;8(1):3155.
    doi: 10.1038/s41598-018-21194-3pmc: PMC5816641pubmed: 29453333google scholar: lookup
  71. Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing.. Sports Med 2003;33(5):381-94.
    doi: 10.2165/00007256-200333050-00004pubmed: 12696985google scholar: lookup
  72. Lim J, Munivez E, Jiang MM, Song IW, Gannon F, Keene DR, Schweitzer R, Lee BH, Joeng KS. mTORC1 Signaling is a Critical Regulator of Postnatal Tendon Development.. Sci Rep 2017 Dec 7;7(1):17175.
    doi: 10.1038/s41598-017-17384-0pmc: PMC5719403pubmed: 29215029google scholar: lookup
  73. Cong XX, Rao XS, Lin JX, Liu XC, Zhang GA, Gao XK, He MY, Shen WL, Fan W, Pioletti D, Zheng LL, Liu HH, Yin Z, Low BC, Schweitzer R, Ouyang H, Chen X, Zhou YT. Activation of AKT-mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells.. Stem Cells 2018 Apr;36(4):527-539.
    doi: 10.1002/stem.2765pubmed: 29315990google scholar: lookup
  74. Kishimoto Y, Ohkawara B, Sakai T, Ito M, Masuda A, Ishiguro N, Shukunami C, Docheva D, Ohno K. Wnt/β-catenin signaling suppresses expressions of Scx, Mkx, and Tnmd in tendon-derived cells.. PLoS One 2017;12(7):e0182051.
    doi: 10.1371/journal.pone.0182051pmc: PMC5531628pubmed: 28750046google scholar: lookup
  75. Bitzer M, von Gersdorff G, Liang D, Dominguez-Rosales A, Beg AA, Rojkind M, Böttinger EP. A mechanism of suppression of TGF-beta/SMAD signaling by NF-kappa B/RelA.. Genes Dev 2000 Jan 15;14(2):187-97.
    pmc: PMC316349pubmed: 10652273
  76. Weng H, Mertens PR, Gressner AM, Dooley S. IFN-gamma abrogates profibrogenic TGF-beta signaling in liver by targeting expression of inhibitory and receptor Smads.. J Hepatol 2007 Feb;46(2):295-303.
    doi: 10.1016/j.jhep.2006.09.014pubmed: 17125875google scholar: lookup
  77. Kim S, Han J, Lee SK, Koo M, Cho DH, Bae SY, Choi MY, Kim JS, Kim JH, Choe JH, Yang JH, Nam SJ, Lee JE. Smad7 acts as a negative regulator of the epidermal growth factor (EGF) signaling pathway in breast cancer cells.. Cancer Lett 2012 Jan 28;314(2):147-54.
    doi: 10.1016/j.canlet.2011.09.024pubmed: 22033246google scholar: lookup
  78. O'Hagan RC, Tozer RG, Symons M, McCormick F, Hassell JA. The activity of the Ets transcription factor PEA3 is regulated by two distinct MAPK cascades.. Oncogene 1996 Sep 19;13(6):1323-33.
    pubmed: 8808707
  79. Paxton JZ, Hagerty P, Andrick JJ, Baar K. Optimizing an intermittent stretch paradigm using ERK1/2 phosphorylation results in increased collagen synthesis in engineered ligaments.. Tissue Eng Part A 2012 Feb;18(3-4):277-84.
    doi: 10.1089/ten.tea.2011.0336pmc: PMC3267962pubmed: 21902469google scholar: lookup
  80. Nishimura K, Blume P, Ohgi S, Sumpio BE. The effect of different frequencies of stretch on human dermal keratinocyte proliferation and survival.. J Surg Res 2009 Jul;155(1):125-31.
    doi: 10.1016/j.jss.2008.07.029pubmed: 19059608google scholar: lookup
  81. Busch F, Mobasheri A, Shayan P, Stahlmann R, Shakibaei M. Sirt-1 is required for the inhibition of apoptosis and inflammatory responses in human tenocytes.. J Biol Chem 2012 Jul 27;287(31):25770-81.
    doi: 10.1074/jbc.M112.355420pmc: PMC3406664pubmed: 22689577google scholar: lookup
  82. Lee SI, Park KH, Kim SJ, Kang YG, Lee YM, Kim EC. Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells.. Clin Exp Immunol 2012 Apr;168(1):113-24.
    doi: 10.1111/j.1365-2249.2011.04549.xpmc: PMC3390502pubmed: 22385246google scholar: lookup
  83. Zhang C, Zhang E, Yang L, Tu W, Lin J, Yuan C, Bunpetch V, Chen X, Ouyang H. Histone deacetylase inhibitor treated cell sheet from mouse tendon stem/progenitor cells promotes tendon repair.. Biomaterials 2018 Jul;172:66-82.
    doi: 10.1016/j.biomaterials.2018.03.043pubmed: 29723756google scholar: lookup
  84. Wang D, Jiang X, Lu A, Tu M, Huang W, Huang P. BMP14 induces tenogenic differentiation of bone marrow mesenchymal stem cells in vitro.. Exp Ther Med 2018 Aug;16(2):1165-1174.
    doi: 10.3892/etm.2018.6293pmc: PMC6090266pubmed: 30116367google scholar: lookup
  85. Zerr P, Palumbo-Zerr K, Huang J, Tomcik M, Sumova B, Distler O, Schett G, Distler JH. Sirt1 regulates canonical TGF-β signalling to control fibroblast activation and tissue fibrosis.. Ann Rheum Dis 2016 Jan;75(1):226-33.
    pubmed: 25180292doi: 10.1136/annrheumdis-2014-205740google scholar: lookup

Citations

This article has been cited 3 times.
  1. Gonzalez RD, Small GW, Green AJ, Akhtari FS, Motsinger-Reif AA, Quintanilha JCF, Havener TM, Reif DM, McLeod HL, Wiltshire T. MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients.. Pharmaceuticals (Basel) 2023 May 17;16(5).
    doi: 10.3390/ph16050757pubmed: 37242540google scholar: lookup
  2. Barrachina L, Arshaghi TE, O'Brien A, Ivanovska A, Barry F. Induced pluripotent stem cells in companion animals: how can we move the field forward?. Front Vet Sci 2023;10:1176772.
    doi: 10.3389/fvets.2023.1176772pubmed: 37180067google scholar: lookup
  3. Hardeland R. Melatonin and the Programming of Stem Cells.. Int J Mol Sci 2022 Feb 10;23(4).
    doi: 10.3390/ijms23041971pubmed: 35216086google scholar: lookup
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