Analyze Diet
BMC musculoskeletal disorders2020; 21(1); 627; doi: 10.1186/s12891-020-03650-2

Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro.

Abstract: Tendon injuries amount to one of the leading causes of career-ending injuries in horses due to the inability for tendon to completely repair and the high reinjury potential. As a result, novel therapeutics are necessary to improve repair with the goal of decreasing leg lameness and potential reinjury. Small leucine-rich repeat proteoglycans (SLRPs), a class of regulatory molecules responsible for collagen organization and maturation, may be one such therapeutic to improve tendon repair. Before SLRP supplementation can occur in vivo, proper evaluation of the effect of these molecules in vitro needs to be assessed. The objective of this study was to evaluate the effectiveness of purified bovine biglycan or decorin on tendon proper and peritenon cell populations in three-dimensional tendon constructs. Methods: Equine tendon proper or peritenon cell seeded fibrin three-dimensional constructs were supplemented with biglycan or decorin at two concentrations (5 nM or 25 nM). The functionality and ultrastructural morphology of the constructs were assessed using biomechanics, collagen content analysis, transmission electron microscopy (TEM), and gene expression by real time - quantitative polymerase chain reaction (RT-qPCR). Results: SLRP supplementation affected both tendon proper and peritenon cells-seeded constructs. With additional SLRPs, material and tensile properties of constructs strengthened, though ultrastructural analyses indicated production of similar-sized or smaller fibrils. Overall expression of tendon markers was bolstered more in peritenon cells supplemented with either SLRP, while supplementation of SLRPs to TP cell-derived constructs demonstrated fewer changes in tendon and extracellular matrix markers. Moreover, relative to non-supplemented tendon proper cell-seeded constructs, SLRP supplementation of the peritenon cells showed increases in mechanical strength, material properties, and collagen content. Conclusions: The SLRP-supplemented peritenon cells produced constructs with greater mechanical and material properties than tendon proper seeded constructs, as well as increased expression of matrix assembly molecules. These findings provide evidence that SLRPs should be further investigated for their potential to improve tendon formation in engineered grafts or post-injury.
Publication Date: 2020-09-23 PubMed ID: 32967653PubMed Central: PMC7513506DOI: 10.1186/s12891-020-03650-2Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • 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.

This research looked at the impact of adding the molecules biglycan or decorin to equine tendon cells in a controlled lab setting. The results showed that these additions improved the formation of tendon-like structures, suggesting a possible therapeutic treatment to enhance tendon repair in horses.

Background

  • The study aimed to address tendon injuries in horses, a major cause of career-ending injuries in these animals. Despite advances in veterinary medicine, complete repair of tendons remains a challenge and reinjury is common, disrupting the horse’s athletic function and causing painful lameness.
  • Researchers are constantly seeking effective ways to improve repair with the aim of minimizing lameness and potential reinjury. This study focused on the potential therapeutic value of small leucine-rich repeat proteoglycans (SLRPs), a class of regulatory molecules that manage collagen organization and maturation. SLRPs are essential to tissue repair and regeneration.

Methodology

  • Before testing the effect of SLRPs in live animals (in vivo), the study first evaluated their effectiveness on laboratory-grown (in vitro) tendons.
  • The researchers introduced purified bovine biglycan or decorin—two kinds of SLRPs—to tendon tissues derived from either tendon proper or peritenon cells in three-dimensional structures.
  • The functionality and ultrastructural morphology of the tendon constructs were then evaluated through several methods, including biomechanics, collagen content analysis, transmission electron microscopy (TEM), and gene expression analysis through real-time quantitative polymerase chain reaction (RT-qPCR).

Results

  • The study found that adding SLRPs to the lab-grown tendon constructs positively affected both tendon proper cells and peritenon cells.
  • SLRP supplementation resulted in brighter material and tensile properties, indicating stronger tissue formation.
  • Moreover, peritenon cell-seeded constructs supplemented with either type of SLRPs showed boosted tendon marker expression relative to non-supplemented tendon proper cell-seeded constructs.
  • SLRP supplementation resulted in increases in mechanical strength, material properties, and collagen content in the peritenon cells when compared with non-supplemented tendon proper cells.

Conclusions

  • The researchers concluded that SLRP-supplemented peritenon cells created tendon constructs with superior mechanical and material properties than those from tendon proper cells.
  • These improved cells also had increased expression of matrix assembly molecules, suggesting increased tissue regeneration potential.
  • Overall, this study provides evidence for further investigation into the use of SLRPs as a possible treatment to improve tendon formation in engineered grafts or post-injury therapeutics.

Cite This Article

APA
Pechanec MY, Boyd TN, Baar K, Mienaltowski MJ. (2020). Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro. BMC Musculoskelet Disord, 21(1), 627. https://doi.org/10.1186/s12891-020-03650-2

Publication

ISSN: 1471-2474
NlmUniqueID: 100968565
Country: England
Language: English
Volume: 21
Issue: 1
Pages: 627
PII: 627

Researcher Affiliations

Pechanec, Monica Y
  • Department of Animal Science, University of California Davis, 2251 Meyer Hall, One Shields Ave, Davis, CA, 95616, USA.
Boyd, Tannah N
  • Department of Animal Science, University of California Davis, 2251 Meyer Hall, One Shields Ave, Davis, CA, 95616, USA.
Baar, Keith
  • Department of Neurobiology, Physiology, and Behavior, University of California Davis, 195 Briggs Hall, One Shields Ave, Davis, CA, 95616, USA.
  • Department of Physiology and Membrane Biology, University of California Davis School of Medicine, 195 Briggs Hall, One Shields Ave, Davis, CA, 95616, USA.
Mienaltowski, Michael J
  • Department of Animal Science, University of California Davis, 2251 Meyer Hall, One Shields Ave, Davis, CA, 95616, USA. mjmienaltowski@ucdavis.edu.

MeSH Terms

  • Animals
  • Biglycan
  • Cattle
  • Collagen
  • Decorin
  • Extracellular Matrix Proteins
  • Horses
  • Tendons

Conflict of Interest Statement

The authors declare that they have no competing interests.

References

This article includes 68 references
  1. Tipton TE, Ray CS, Hand DR. Superficial digital flexor tendonitis in cutting horses: 19 cases (2007-2011).. J Am Vet Med Assoc 2013 Oct 15;243(8):1162-5.
    pubmed: 24094264doi: 10.2460/javma.243.8.1162google scholar: lookup
  2. Thorpe CT, Clegg PD, Birch HL. A review of tendon injury: why is the equine superficial digital flexor tendon most at risk?. Equine Vet J 2010 Mar;42(2):174-80.
    pubmed: 20156256doi: 10.2746/042516409x480395google scholar: lookup
  3. Jacobson E, Dart AJ, Mondori T, Horadogoda N, Jeffcott LB, Little CB, Smith MM. Focal experimental injury leads to widespread gene expression and histologic changes in equine flexor tendons.. PLoS One 2015;10(4):e0122220.
  4. Halper J. Connective tissue disorders in domestic animals.. Adv Exp Med Biol 2014;802:231-40.
    pubmed: 24443030doi: 10.1007/978-94-007-7893-1_14google scholar: lookup
  5. Mienaltowski MJ, Birk DE. Structure, physiology, and biochemistry of collagens.. Adv Exp Med Biol 2014;802:5-29.
    pubmed: 24443018doi: 10.1007/978-94-007-7893-1_2google scholar: lookup
  6. Dourte LM, Pathmanathan L, Mienaltowski MJ, Jawad AF, Birk DE, Soslowsky LJ. Mechanical, compositional, and structural properties of the mouse patellar tendon with changes in biglycan gene expression.. J Orthop Res 2013 Sep;31(9):1430-7.
    pmc: PMC3801205pubmed: 23592048doi: 10.1002/jor.22372google scholar: lookup
  7. Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Kumar A, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ. The injury response of aged tendons in the absence of biglycan and decorin.. Matrix Biol 2014 Apr;35:232-8.
  8. Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Satchell L, Kumar A, Pathmanathan L, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ. Decorin expression is important for age-related changes in tendon structure and mechanical properties.. Matrix Biol 2013 Jan;32(1):3-13.
  9. Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Satchell L, Kumar A, Pathmanathan L, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ. The tendon injury response is influenced by decorin and biglycan.. Ann Biomed Eng 2014 Mar;42(3):619-30.
    pmc: PMC3943488pubmed: 24072490doi: 10.1007/s10439-013-0915-2google scholar: lookup
  10. Mienaltowski MJ, Dunkman AA, Buckley MR, Beason DP, Adams SM, Birk DE, Soslowsky LJ. Injury response of geriatric mouse patellar tendons.. J Orthop Res 2016 Jul;34(7):1256-63.
    pmc: PMC4919222pubmed: 26704368doi: 10.1002/jor.23144google scholar: lookup
  11. Lechner BE, Lim JH, Mercado ML, Fallon JR. Developmental regulation of biglycan expression in muscle and tendon.. Muscle Nerve 2006 Sep;34(3):347-55.
    pubmed: 16810681doi: 10.1002/mus.20596google scholar: lookup
  12. Robinson KA, Sun M, Barnum CE, Weiss SN, Huegel J, Shetye SS, Lin L, Saez D, Adams SM, Iozzo RV, Soslowsky LJ, Birk DE. Decorin and biglycan are necessary for maintaining collagen fibril structure, fiber realignment, and mechanical properties of mature tendons.. Matrix Biol 2017 Dec;64:81-93.
  13. 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
  14. Frey H, Schroeder N, Manon-Jensen T, Iozzo RV, Schaefer L. Biological interplay between proteoglycans and their innate immune receptors in inflammation.. FEBS J 2013 May;280(10):2165-79.
    pmc: PMC3651745pubmed: 23350913doi: 10.1111/febs.12145google scholar: lookup
  15. Ingraham JM, Hauck RM, Ehrlich HP. Is the tendon embryogenesis process resurrected during tendon healing?. Plast Reconstr Surg 2003 Sep;112(3):844-54.
  16. Dyment NA, Liu CF, Kazemi N, Aschbacher-Smith LE, Kenter K, Breidenbach AP, Shearn JT, Wylie C, Rowe DW, Butler DL. The paratenon contributes to scleraxis-expressing cells during patellar tendon healing.. PLoS One 2013;8(3):e59944.
  17. Jelinsky SA, Archambault J, Li L, Seeherman H. Tendon-selective genes identified from rat and human musculoskeletal tissues.. J Orthop Res 2010 Mar;28(3):289-97.
    pubmed: 19780194doi: 10.1002/jor.20999google scholar: lookup
  18. Mienaltowski MJ, Adams SM, Birk DE. Regional differences in stem cell/progenitor cell populations from the mouse achilles tendon.. Tissue Eng Part A 2013 Jan;19(1-2):199-210.
    pmc: PMC3530943pubmed: 22871316doi: 10.1089/ten.tea.2012.0182google scholar: lookup
  19. Mienaltowski MJ, Cánovas A, Fates VA, Hampton AR, Pechanec MY, Islas-Trejo A, Medrano JF. Transcriptome profiles of isolated murine Achilles tendon proper- and peritenon-derived progenitor cells.. J Orthop Res 2019 Jun;37(6):1409-1418.
    pubmed: 29926971doi: 10.1002/jor.24076google scholar: lookup
  20. Mienaltowski MJ, Adams SM, Birk DE. Tendon proper- and peritenon-derived progenitor cells have unique tenogenic properties.. Stem Cell Res Ther 2014 Jul 8;5(4):86.
    pmc: PMC4230637pubmed: 25005797doi: 10.1186/scrt475google scholar: lookup
  21. Pechanec MY, Lee-Barthel A, Baar K, Mienaltowski MJ. Evaluation and optimization of a three-dimensional construct model for equine superficial digital flexor tendon. J Equine Vet Sci 2018;71:90–97.
  22. Paxton JZ, Grover LM, Baar K. Engineering an in vitro model of a functional ligament from bone to bone.. Tissue Eng Part A 2010 Nov;16(11):3515-25.
    pubmed: 20593972doi: 10.1089/ten.tea.2010.0039google scholar: lookup
  23. 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.
  24. Amenta AR, Yilmaz A, Bogdanovich S, McKechnie BA, Abedi M, Khurana TS, Fallon JR. Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice.. Proc Natl Acad Sci U S A 2011 Jan 11;108(2):762-7.
    pmc: PMC3021068pubmed: 21187385doi: 10.1073/pnas.1013067108google scholar: lookup
  25. Csont T, Görbe A, Bereczki E, Szunyog A, Aypar E, Tóth ME, Varga ZV, Csonka C, Fülöp F, Sántha M, Ferdinandy P. Biglycan protects cardiomyocytes against hypoxia/reoxygenation injury: role of nitric oxide.. J Mol Cell Cardiol 2010 Apr;48(4):649-52.
    pubmed: 20096286doi: 10.1016/j.yjmcc.2010.01.013google scholar: lookup
  26. Reese SP, Underwood CJ, Weiss JA. Effects of decorin proteoglycan on fibrillogenesis, ultrastructure, and mechanics of type I collagen gels.. Matrix Biol 2013 Oct-Nov;32(7-8):414-23.
  27. Lee-Barthel A, Baar K, West DWD. Treatment of Ligament Constructs with Exercise-conditioned Serum: A Translational Tissue Engineering Model.. J Vis Exp 2017 Jun 11;(124).
    pmc: PMC5608388pubmed: 28654031doi: 10.3791/55339google scholar: lookup
  28. 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.
    pubmed: 18262777doi: 10.1016/j.matbio.2007.11.006google scholar: lookup
  29. Calve S, Dennis RG, Kosnik PE 2nd, Baar K, Grosh K, Arruda EM. Engineering of functional tendon.. Tissue Eng 2004 May-Jun;10(5-6):755-61.
    pubmed: 15265292doi: 10.1089/1076327041348464google scholar: lookup
  30. Larkin LM, Calve S, Kostrominova TY, Arruda EM. Structure and functional evaluation of tendon-skeletal muscle constructs engineered in vitro.. Tissue Eng 2006 Nov;12(11):3149-58.
    pmc: PMC2798802pubmed: 17518629doi: 10.1089/ten.2006.12.3149google scholar: lookup
  31. WOESSNER JF Jr. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid.. Arch Biochem Biophys 1961 May;93:440-7.
    pubmed: 13786180doi: 10.1016/0003-9861(61)90291-0google scholar: lookup
  32. Edwards CA, O'Brien WD Jr. Modified assay for determination of hydroxyproline in a tissue hydrolyzate.. Clin Chim Acta 1980 Jun 10;104(2):161-7.
    pubmed: 7389130doi: 10.1016/0009-8981(80)90192-8google scholar: lookup
  33. Mushran SP, Agrawal MC, Prasad B. Mechanism of oxidation by chloramine-T. Part I. Oxidation of α-hydroxy-acids. J Chem Soc. B 1971;Part I:1712–4.
  34. Creemers LB, Jansen DC, van Veen-Reurings A, van den Bos T, Everts V. Microassay for the assessment of low levels of hydroxyproline.. Biotechniques 1997 Apr;22(4):656-8.
    pubmed: 9105617doi: 10.2144/97224bm19google scholar: lookup
  35. Birk DE, Trelstad RL. Extracellular compartments in matrix morphogenesis: collagen fibril, bundle, and lamellar formation by corneal fibroblasts.. J Cell Biol 1984 Dec;99(6):2024-33.
    pmc: PMC2113579pubmed: 6542105doi: 10.1083/jcb.99.6.2024google scholar: lookup
  36. Birk DE, Trelstad RL. Extracellular compartments in tendon morphogenesis: collagen fibril, bundle, and macroaggregate formation.. J Cell Biol 1986 Jul;103(1):231-40.
    pmc: PMC2113791pubmed: 3722266doi: 10.1083/jcb.103.1.231google scholar: lookup
  37. Mienaltowski MJ, Huang L, Frisbie DD, McIlwraith CW, Stromberg AJ, Bathke AC, Macleod JN. Transcriptional profiling differences for articular cartilage and repair tissue in equine joint surface lesions.. BMC Med Genomics 2009 Sep 14;2:60.
    pmc: PMC2751772pubmed: 19751507doi: 10.1186/1755-8794-2-60google scholar: lookup
  38. Mienaltowski MJ, Huang L, Stromberg AJ, MacLeod JN. Differential gene expression associated with postnatal equine articular cartilage maturation.. BMC Musculoskelet Disord 2008 Nov 5;9:149.
    pmc: PMC2585085pubmed: 18986532doi: 10.1186/1471-2474-9-149google scholar: lookup
  39. 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.
  40. Scott EY, Mansour T, Bellone RR, Brown CT, Mienaltowski MJ, Penedo MC, Ross PJ, Valberg SJ, Murray JD, Finno CJ. Identification of long non-coding RNA in the horse transcriptome.. BMC Genomics 2017 Jul 4;18(1):511.
    pmc: PMC5496257pubmed: 28676104doi: 10.1186/s12864-017-3884-2google scholar: lookup
  41. Mansour TA, Scott EY, Finno CJ, Bellone RR, Mienaltowski MJ, Penedo MC, Ross PJ, Valberg SJ, Murray JD, Brown CT. Tissue resolved, gene structure refined equine transcriptome.. BMC Genomics 2017 Jan 20;18(1):103.
    pmc: PMC5251313pubmed: 28107812doi: 10.1186/s12864-016-3451-2google scholar: lookup
  42. Ramakers C, Ruijter JM, Deprez RH, Moorman AF. Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data.. Neurosci Lett 2003 Mar 13;339(1):62-6.
    pubmed: 12618301doi: 10.1016/s0304-3940(02)01423-4google scholar: lookup
  43. Schefe JH, Lehmann KE, Buschmann IR, Unger T, Funke-Kaiser H. Quantitative real-time RT-PCR data analysis: current concepts and the novel "gene expression's CT difference" formula.. J Mol Med (Berl) 2006 Nov;84(11):901-10.
    pubmed: 16972087doi: 10.1007/s00109-006-0097-6google scholar: lookup
  44. Wilcoxon F. Individual comparisons by ranking methods. Biom Bull 1945;1(6):80–83.
  45. Bland JM, Altman DG. One and two sided tests of significance.. BMJ 1994 Jul 23;309(6949):248.
    pmc: PMC2540725pubmed: 8069143doi: 10.1136/bmj.309.6949.248google scholar: lookup
  46. Murphy R. On the use of one-sided statistical tests in biomedical research.. Clin Exp Pharmacol Physiol 2018 Jan;45(1):109-114.
    pubmed: 28323356doi: 10.1111/1440-1681.12754google scholar: lookup
  47. Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility.. J Cell Biol 1997 Feb 10;136(3):729-43.
    pmc: PMC2134287pubmed: 9024701doi: 10.1083/jcb.136.3.729google scholar: lookup
  48. Wadhwa S, Embree MC, Kilts T, Young MF, Ameye LG. Accelerated osteoarthritis in the temporomandibular joint of biglycan/fibromodulin double-deficient mice.. Osteoarthritis Cartilage 2005 Sep;13(9):817-27.
    pubmed: 16006154doi: 10.1016/j.joca.2005.04.016google scholar: lookup
  49. Parisuthiman D, Mochida Y, Duarte WR, Yamauchi M. Biglycan modulates osteoblast differentiation and matrix mineralization.. J Bone Miner Res 2005 Oct;20(10):1878-86.
    pubmed: 16160746doi: 10.1359/jbmr.050612google scholar: lookup
  50. Han B, Li Q, Wang C, Patel P, Adams SM, Doyran B, Nia HT, Oftadeh R, Zhou S, Li CY, Liu XS, Lu XL, Enomoto-Iwamoto M, Qin L, Mauck RL, Iozzo RV, Birk DE, Han L. Decorin Regulates the Aggrecan Network Integrity and Biomechanical Functions of Cartilage Extracellular Matrix.. ACS Nano 2019 Oct 22;13(10):11320-11333.
    pmc: PMC6892632pubmed: 31550133doi: 10.1021/acsnano.9b04477google scholar: lookup
  51. Delalande A, Gosselin MP, Suwalski A, Guilmain W, Leduc C, Berchel M, Jaffrès PA, Baril P, Midoux P, Pichon C. Enhanced Achilles tendon healing by fibromodulin gene transfer.. Nanomedicine 2015 Oct;11(7):1735-44.
    pubmed: 26048315doi: 10.1016/j.nano.2015.05.004google scholar: lookup
  52. Ye Y, Hu W, Guo F, Zhang W, Wang J, Chen A. Glycosaminoglycan chains of biglycan promote bone morphogenetic protein-4-induced osteoblast differentiation.. Int J Mol Med 2012 Nov;30(5):1075-80.
    pubmed: 22895561doi: 10.3892/ijmm.2012.1091google scholar: lookup
  53. Berendsen AD, Fisher LW, Kilts TM, Owens RT, Robey PG, Gutkind JS, Young MF. Modulation of canonical Wnt signaling by the extracellular matrix component biglycan.. Proc Natl Acad Sci U S A 2011 Oct 11;108(41):17022-7.
    pmc: PMC3193219pubmed: 21969569doi: 10.1073/pnas.1110629108google scholar: lookup
  54. Schönherr E, Levkau B, Schaefer L, Kresse H, Walsh K. Decorin affects endothelial cells by Akt-dependent and -independent pathways.. Ann N Y Acad Sci 2002 Nov;973:149-52.
  55. Mohan RR, Tripathi R, Sharma A, Sinha PR, Giuliano EA, Hesemann NP, Chaurasia SS. Decorin antagonizes corneal fibroblast migration via caveolae-mediated endocytosis of epidermal growth factor receptor.. Exp Eye Res 2019 Mar;180:200-207.
    pubmed: 30611736doi: 10.1016/j.exer.2019.01.001google scholar: lookup
  56. Geng Y, McQuillan D, Roughley PJ. SLRP interaction can protect collagen fibrils from cleavage by collagenases.. Matrix Biol 2006 Oct;25(8):484-91.
    pubmed: 16979885doi: 10.1016/j.matbio.2006.08.259google scholar: lookup
  57. Meij JT, Carlson EC, Wang L, Liu CY, Jester JV, Birk DE, Kao WW. Targeted expression of a lumican transgene rescues corneal deficiencies in lumican-null mice.. Mol Vis 2007 Oct 18;13:2012-8.
    pubmed: 17982425
  58. Jiang W, Ting K, Lee S, Zara JN, Song R, Li C, Chen E, Zhang X, Zhao Z, Soo C, Zheng Z. Fibromodulin reduces scar size and increases scar tensile strength in normal and excessive-mechanical-loading porcine cutaneous wounds.. J Cell Mol Med 2018 Apr;22(4):2510-2513.
    pmc: PMC5867110pubmed: 29392829doi: 10.1111/jcmm.13516google scholar: lookup
  59. Gáspár R, Pipicz M, Hawchar F, Kovács D, Djirackor L, Görbe A, Varga ZV, Kiricsi M, Petrovski G, Gácser A, Csonka C, Csont T. The cytoprotective effect of biglycan core protein involves Toll-like receptor 4 signaling in cardiomyocytes.. J Mol Cell Cardiol 2016 Oct;99:138-150.
    pubmed: 27515282doi: 10.1016/j.yjmcc.2016.08.006google scholar: lookup
  60. Barnette DN, Hulin A, Ahmed AS, Colige AC, Azhar M, Lincoln J. Tgfβ-Smad and MAPK signaling mediate scleraxis and proteoglycan expression in heart valves.. J Mol Cell Cardiol 2013 Dec;65:137-46.
    pmc: PMC3869408pubmed: 24157418doi: 10.1016/j.yjmcc.2013.10.007google scholar: lookup
  61. Farhat YM, Al-Maliki AA, Chen T, Juneja SC, Schwarz EM, O'Keefe RJ, Awad HA. Gene expression analysis of the pleiotropic effects of TGF-β1 in an in vitro model of flexor tendon healing.. PLoS One 2012;7(12):e51411.
  62. Berendsen AD, Pinnow EL, Maeda A, Brown AC, McCartney-Francis N, Kram V, Owens RT, Robey PG, Holmbeck K, de Castro LF, Kilts TM, Young MF. Biglycan modulates angiogenesis and bone formation during fracture healing.. Matrix Biol 2014 Apr;35:223-31.
  63. Neill T, Painter H, Buraschi S, Owens RT, Lisanti MP, Schaefer L, Iozzo RV. Decorin antagonizes the angiogenic network: concurrent inhibition of Met, hypoxia inducible factor 1α, vascular endothelial growth factor A, and induction of thrombospondin-1 and TIMP3.. J Biol Chem 2012 Feb 17;287(8):5492-506.
    pmc: PMC3285326pubmed: 22194599doi: 10.1074/jbc.m111.283499google scholar: lookup
  64. Korntner S, Lehner C, Gehwolf R, Wagner A, Grütz M, Kunkel N, Tempfer H, Traweger A. Limiting angiogenesis to modulate scar formation.. Adv Drug Deliv Rev 2019 Jun;146:170-189.
    pubmed: 29501628doi: 10.1016/j.addr.2018.02.010google scholar: lookup
  65. DiPietro LA. Angiogenesis and scar formation in healing wounds.. Curr Opin Rheumatol 2013 Jan;25(1):87-91.
    pubmed: 23114588doi: 10.1097/bor.0b013e32835b13b6google scholar: lookup
  66. Cadby JA, Buehler E, Godbout C, van Weeren PR, Snedeker JG. Differences between the cell populations from the peritenon and the tendon core with regard to their potential implication in tendon repair.. PLoS One 2014;9(3):e92474.
  67. Costa-Almeida R, Gonçalves AI, Gershovich P, Rodrigues MT, Reis RL, Gomes ME. Tendon stem cell niche. .
  68. Dyment NA, Hagiwara Y, Matthews BG, Li Y, Kalajzic I, Rowe DW. Lineage tracing of resident tendon progenitor cells during growth and natural healing.. PLoS One 2014;9(4):e96113.

Citations

This article has been cited 12 times.
  1. Nam HY, Draman Yusof MR, Kamarul T. Adipose and Bone Marrow Derived-Mesenchymal Stromal Cells Express Similar Tenogenic Expression Levels when Subjected to Mechanical Uniaxial Stretching In Vitro. Stem Cells Int 2023;2023:4907230.
    doi: 10.1155/2023/4907230pubmed: 36756494google scholar: lookup
  2. Chen Z, Chen P, Zheng M, Gao J, Liu D, Wang A, Zheng Q, Leys T, Tai A, Zheng M. Challenges and perspectives of tendon-derived cell therapy for tendinopathy: from bench to bedside. Stem Cell Res Ther 2022 Sep 2;13(1):444.
    doi: 10.1186/s13287-022-03113-6pubmed: 36056395google scholar: lookup
  3. Chen SH, Chen ZY, Lin YH, Chen SH, Chou PY, Kao HK, Lin FH. Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons. Int J Mol Sci 2021 Nov 16;22(22).
    doi: 10.3390/ijms222212373pubmed: 34830254google scholar: lookup
  4. Appunni S, Rubens M, Ramamoorthy V, Anand V, Khandelwal M, Sharma A. Biglycan: an emerging small leucine-rich proteoglycan (SLRP) marker and its clinicopathological significance. Mol Cell Biochem 2021 Nov;476(11):3935-3950.
    doi: 10.1007/s11010-021-04216-zpubmed: 34181183google scholar: lookup
  5. Tao M, Ruan X, Yu J, Dong Q, Luo W, Zhang W, Tian M, Hou X, Hu L, Zhao J, Li D, Hao J, Wei S, Zheng X, Gao M. Enhancer-mediated NR2F2 recruitment activates BGN to promote tumor growth and shape tumor microenvironment in papillary thyroid cancer. Theranostics 2026;16(1):298-324.
    doi: 10.7150/thno.113712pubmed: 41328346google scholar: lookup
  6. Łosińska K, Rzeszutko-Bełzowska A, Ficek K, September AV. Are decorin gene variants associated with anterior cruciate ligament rupture susceptibility?. Biol Sport 2025 Oct;42(4):333-343.
    doi: 10.5114/biolsport.2025.152112pubmed: 41048225google scholar: lookup
  7. Hordé M, Fouchard J, Palacios LG, Laffray X, Blavet C, Béréziat V, Lagathu C, Gaut L, Duprez D, Havis E. Human adipose stromal cells differentiate towards a tendon phenotype with adapted visco-elastic properties in a 3D-culture system. Biol Open 2025 May 15;14(5).
    doi: 10.1242/bio.061911pubmed: 40271554google scholar: lookup
  8. Di Francesco D, Marcello E, Casarella S, Copes F, Chevallier P, Carmagnola I, Mantovani D, Boccafoschi F. Characterization of a decellularized pericardium extracellular matrix hydrogel for regenerative medicine: insights on animal-to-animal variability. Front Bioeng Biotechnol 2024;12:1452965.
    doi: 10.3389/fbioe.2024.1452965pubmed: 39205858google scholar: lookup
  9. Avey AM, Valdez O, Baar K. Characterization of an in vitro engineered ligament model. Matrix Biol Plus 2024 Feb;21:100140.
    doi: 10.1016/j.mbplus.2023.100140pubmed: 38235356google scholar: lookup
  10. Mienaltowski MJ, Callahan M, Gonzales NL, Wong A. Examining the Potential of Vitamin C Supplementation in Tissue-Engineered Equine Superficial Digital Flexor Tendon Constructs. Int J Mol Sci 2023 Dec 4;24(23).
    doi: 10.3390/ijms242317098pubmed: 38069418google scholar: lookup
  11. Hjortshoej MH, Aagaard P, Storgaard CD, Juneja H, Lundbye-Jensen J, Magnusson SP, Couppé C. Hormonal, immune, and oxidative stress responses to blood flow-restricted exercise. Acta Physiol (Oxf) 2023 Oct;239(2):e14030.
    doi: 10.1111/apha.14030pubmed: 37732509google scholar: lookup
  12. Gesteira TF, Verma S, Coulson-Thomas VJ. Small leucine rich proteoglycans: Biology, function and their therapeutic potential in the ocular surface. Ocul Surf 2023 Jul;29:521-536.
    doi: 10.1016/j.jtos.2023.06.013pubmed: 37355022google scholar: lookup