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Home / Equine Research Bank / Int J Mol Sci / RNA Interference and BMP-2 Stimulation Allows Equine Chondro...
International journal of molecular sciences2017; 18(9); 1842; doi: 10.3390/ijms18091842

RNA Interference and BMP-2 Stimulation Allows Equine Chondrocytes Redifferentiation in 3D-Hypoxia Cell Culture Model: Application for Matrix-Induced Autologous Chondrocyte Implantation.

Abstract: As in humans, osteoarthritis (OA) causes considerable economic loss to the equine industry. New hopes for cartilage repair have emerged with the matrix-associated autologous chondrocyte implantation (MACI). Nevertheless, its limitation is due to the dedifferentiation occurring during the chondrocyte amplification phase, leading to the loss of its capacity to produce a hyaline extracellular matrix (ECM). To enhance the MACI therapy efficiency, we have developed a strategy for chondrocyte redifferentiation, and demonstrated its feasibility in the equine model. Thus, to mimic the cartilage microenvironment, the equine dedifferentiated chondrocytes were cultured in type I/III collagen sponges for 7 days under hypoxia in the presence of BMP-2. In addition, chondrocytes were transfected by siRNA targeting and mRNAs, which are overexpressed during dedifferentiation and OA. To investigate the quality of the neo-synthesized ECM, specific and atypical cartilage markers were evaluated by RT-qPCR and Western blot. Our results show that the combination of 3D hypoxia cell culture, BMP-2 (Bone morphogenetic protein-2), and RNA interference, increases the chondrocytes functional indexes (/, /), leading to an effective chondrocyte redifferentiation. These data represent a proof of concept for this process of application, in vitro, in the equine model, and will lead to the improvement of the MACI efficiency for cartilage tissue engineering therapy in preclinical/clinical trials, both in equine and human medicine.
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Publication Date: 2017-08-24 PubMed ID: 28837082PubMed Central: PMC5618491DOI: 10.3390/ijms18091842Google Scholar: Lookup
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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 presents a study on the use of RNA Interference and BMP-2 stimulation to enhance the effectiveness of a cartilage repair treatment known as Matrix-Associated Autologous Chondrocyte Implantation (MACI). The study uses an equine model to show that this approach can help redifferentiate chondrocytes, which are cells in the cartilage that lose their function during OA and MACI.

Objective of the Study

  • The study aimed to develop a strategy to redifferentiate chondrocytes, which usually undergo dedifferentiation during MACI. Dedifferentiation refers to the loss of specific function in cells, in this case, the chondrocytes lose their ability to produce hyaline extracellular matrix (ECM), an essential substance for healthy cartilage.

Methodology

  • The researchers cultured equine dedifferentiated chondrocytes in type I/III collagen sponges for 7 days under conditions of low oxygen (hypoxia), which mimic the natural environment of the cartilage. They also stimulated the cells with Bone Morphogenetic Protein-2 (BMP-2).
  • In addition, the chondrocytes were transfected with small interfering RNA (siRNA) that target specific mRNAs, which are overexpressed during chondrocyte dedifferentiation and osteoarthritis (OA).
  • The researchers then assessed the quality of the newly synthesized ECM through specific and atypical cartilage markers, evaluated via RT-qPCR and Western blot tests.

Results

  • The results showed that the combination of 3D hypoxia cell culture, BMP-2 (Bone morphogenetic protein-2), and RNA interference increases the functional indexes of chondrocytes, leading to effective redifferentiation of the cells.

Conclusion

  • The data provided is a proof of concept for applying this strategy in vitro in the equine model, with the potential to improve the efficiency of MACI for cartilage tissue engineering therapy. This has implications for preclinical and clinical trials, not only in equine medicine, but also in human medicine, particularly in the treatment of OA.

Cite This Article

APA
Rakic R, Bourdon B, Hervieu M, Branly T, Legendre F, Saulnier N, Audigié F, Maddens S, Demoor M, Galera P. (2017). RNA Interference and BMP-2 Stimulation Allows Equine Chondrocytes Redifferentiation in 3D-Hypoxia Cell Culture Model: Application for Matrix-Induced Autologous Chondrocyte Implantation. Int J Mol Sci, 18(9), 1842. https://doi.org/10.3390/ijms18091842

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 18
Issue: 9
PII: 1842

Researcher Affiliations

Rakic, Rodolphe
  • Normandie Université, UNICAEN, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT), équipe Microenvironnement des Pathologies Dégénératives et Fibrotiques (MIPDF), EA 4652/BIOTARGEN EA 7450, UFR Santé, Université de Caen Normandie, 14032 Caen, France. rodolphe.rakic@gmail.com.
  • Vetbiobank, 1 Avenue Bourgelat, 69280 Marcy l'Etoile, France. rodolphe.rakic@gmail.com.
Bourdon, Bastien
  • Normandie Université, UNICAEN, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT), équipe Microenvironnement des Pathologies Dégénératives et Fibrotiques (MIPDF), EA 4652/BIOTARGEN EA 7450, UFR Santé, Université de Caen Normandie, 14032 Caen, France. bourdon.bas@laposte.net.
Hervieu, Magalie
  • Normandie Université, UNICAEN, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT), équipe Microenvironnement des Pathologies Dégénératives et Fibrotiques (MIPDF), EA 4652/BIOTARGEN EA 7450, UFR Santé, Université de Caen Normandie, 14032 Caen, France. magalie.hervieu@gmail.com.
Branly, Thomas
  • Normandie Université, UNICAEN, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT), équipe Microenvironnement des Pathologies Dégénératives et Fibrotiques (MIPDF), EA 4652/BIOTARGEN EA 7450, UFR Santé, Université de Caen Normandie, 14032 Caen, France. tbranly@gmail.com.
Legendre, Florence
  • Normandie Université, UNICAEN, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT), équipe Microenvironnement des Pathologies Dégénératives et Fibrotiques (MIPDF), EA 4652/BIOTARGEN EA 7450, UFR Santé, Université de Caen Normandie, 14032 Caen, France. florence.legendre@unicaen.fr.
Saulnier, Nathalie
  • Vetbiobank, 1 Avenue Bourgelat, 69280 Marcy l'Etoile, France. n.saulnier@vetbiobank.com.
Audigié, Fabrice
  • Imaging and Research Centre of Equine Locomotor Disorders (CIRALE, 14430 Goustranville, France), Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort, France. fabrice.audigie@vet-alfort.fr.
Maddens, Stéphane
  • Vetbiobank, 1 Avenue Bourgelat, 69280 Marcy l'Etoile, France. s.maddens@vetbiobank.com.
Demoor, Magali
  • Normandie Université, UNICAEN, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT), équipe Microenvironnement des Pathologies Dégénératives et Fibrotiques (MIPDF), EA 4652/BIOTARGEN EA 7450, UFR Santé, Université de Caen Normandie, 14032 Caen, France. magali.demoor@unicaen.fr.
Galera, Philippe
  • Normandie Université, UNICAEN, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT), équipe Microenvironnement des Pathologies Dégénératives et Fibrotiques (MIPDF), EA 4652/BIOTARGEN EA 7450, UFR Santé, Université de Caen Normandie, 14032 Caen, France. philippe.galera@unicaen.fr.

MeSH Terms

  • Animals
  • Biomarkers
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Morphogenetic Protein 2 / pharmacology
  • Cartilage, Articular / cytology
  • Cartilage, Articular / metabolism
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Hypoxia / genetics
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Collagen Type I / metabolism
  • Collagen Type III / metabolism
  • Extracellular Matrix / metabolism
  • Horses
  • Phenotype
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Tissue Engineering

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 68 references
  1. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Joint Res 2012 Nov;1(11):297-309.
    doi: 10.1302/2046-3758.111.2000132pmc: PMC3626203pubmed: 23610661google scholar: lookup
  2. McIlwraith CW, Frisbie DD, Kawcak CE, Fuller CJ, Hurtig M, Cruz A. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the horse.. Osteoarthritis Cartilage 2010 Oct;18 Suppl 3:S93-105.
    doi: 10.1016/j.joca.2010.05.031pubmed: 20864027google scholar: lookup
  3. Oke SL, McIlwraith CW. Review of the economic impact of osteoarthritis and oral joint-health supplements in horses. Proceedings of the 56th Annual Convention of the American Association of Equine Practitioners; Baltimore, MD, USA. 4–8 December 2010; pp. 12–16.
  4. Aigner T, Cook JL, Gerwin N, Glasson SS, Laverty S, Little CB, McIlwraith W, Kraus VB. Histopathology atlas of animal model systems - overview of guiding principles.. Osteoarthritis Cartilage 2010 Oct;18 Suppl 3:S2-6.
    doi: 10.1016/j.joca.2010.07.013pubmed: 20864020google scholar: lookup
  5. Marlovits S, Zeller P, Singer P, Resinger C, Vécsei V. Cartilage repair: generations of autologous chondrocyte transplantation.. Eur J Radiol 2006 Jan;57(1):24-31.
    doi: 10.1016/j.ejrad.2005.08.009pubmed: 16188417google scholar: lookup
  6. Bartlett W, Skinner JA, Gooding CR, Carrington RW, Flanagan AM, Briggs TW, Bentley G. Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study.. J Bone Joint Surg Br 2005 May;87(5):640-5.
    doi: 10.1302/0301-620X.87B5.15905pubmed: 15855365google scholar: lookup
  7. Brittberg M. Autologous chondrocyte implantation--technique and long-term follow-up.. Injury 2008 Apr;39 Suppl 1:S40-9.
    doi: 10.1016/j.injury.2008.01.040pubmed: 18313471google scholar: lookup
  8. Moran CJ, Ramesh A, Brama PA, O'Byrne JM, O'Brien FJ, Levingstone TJ. The benefits and limitations of animal models for translational research in cartilage repair.. J Exp Orthop 2016 Dec;3(1):1.
    doi: 10.1186/s40634-015-0037-xpmc: PMC4703594pubmed: 26915001google scholar: lookup
  9. Nixon AJ, Rickey E, Butler TJ, Scimeca MS, Moran N, Matthews GL. A chondrocyte infiltrated collagen type I/III membrane (MACI® implant) improves cartilage healing in the equine patellofemoral joint model.. Osteoarthritis Cartilage 2015 Apr;23(4):648-60.
    doi: 10.1016/j.joca.2014.12.021pubmed: 25575968google scholar: lookup
  10. Griffin DJ, Bonnevie ED, Lachowsky DJ, Hart JC, Sparks HD, Moran N, Matthews G, Nixon AJ, Cohen I, Bonassar LJ. Mechanical characterization of matrix-induced autologous chondrocyte implantation (MACI®) grafts in an equine model at 53 weeks.. J Biomech 2015 Jul 16;48(10):1944-9.
    doi: 10.1016/j.jbiomech.2015.04.010pubmed: 25920896google scholar: lookup
  11. Ortved KF, Nixon AJ. Cell-based cartilage repair strategies in the horse.. Vet J 2016 Feb;208:1-12.
    doi: 10.1016/j.tvjl.2015.10.027pubmed: 26702950google scholar: lookup
  12. Benya PD, Padilla SR, Nimni ME. Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture.. Cell 1978 Dec;15(4):1313-21.
    doi: 10.1016/0092-8674(78)90056-9pubmed: 729001google scholar: lookup
  13. Marlovits S, Hombauer M, Truppe M, Vècsei V, Schlegel W. Changes in the ratio of type-I and type-II collagen expression during monolayer culture of human chondrocytes.. J Bone Joint Surg Br 2004 Mar;86(2):286-95.
    doi: 10.1302/0301-620X.86B2.14918pubmed: 15046449google scholar: lookup
  14. Claus S, Mayer N, Aubert-Foucher E, Chajra H, Perrier-Groult E, Lafont J, Piperno M, Damour O, Mallein-Gerin F. Cartilage-characteristic matrix reconstruction by sequential addition of soluble factors during expansion of human articular chondrocytes and their cultivation in collagen sponges.. Tissue Eng Part C Methods 2012 Feb;18(2):104-12.
    doi: 10.1089/ten.tec.2011.0259pubmed: 21933021google scholar: lookup
  15. Schnabel M, Marlovits S, Eckhoff G, Fichtel I, Gotzen L, Vécsei V, Schlegel J. Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture.. Osteoarthritis Cartilage 2002 Jan;10(1):62-70.
    doi: 10.1053/joca.2001.0482pubmed: 11795984google scholar: lookup
  16. Kiani C, Chen L, Wu YJ, Yee AJ, Yang BB. Structure and function of aggrecan.. Cell Res 2002 Mar;12(1):19-32.
    doi: 10.1038/sj.cr.7290106pubmed: 11942407google scholar: lookup
  17. Lin Z, Fitzgerald JB, Xu J, Willers C, Wood D, Grodzinsky AJ, Zheng MH. Gene expression profiles of human chondrocytes during passaged monolayer cultivation.. J Orthop Res 2008 Sep;26(9):1230-7.
    doi: 10.1002/jor.20523pubmed: 18404652google scholar: lookup
  18. Blaise R, Mahjoub M, Salvat C, Barbe U, Brou C, Corvol MT, Savouret JF, Rannou F, Berenbaum F, Bausero P. Involvement of the Notch pathway in the regulation of matrix metalloproteinase 13 and the dedifferentiation of articular chondrocytes in murine cartilage.. Arthritis Rheum 2009 Feb;60(2):428-39.
    doi: 10.1002/art.24250pubmed: 19180482google scholar: lookup
  19. Pelttari K, Lorenz H, Boeuf S, Templin MF, Bischel O, Goetzke K, Hsu HY, Steck E, Richter W. Secretion of matrix metalloproteinase 3 by expanded articular chondrocytes as a predictor of ectopic cartilage formation capacity in vivo.. Arthritis Rheum 2008 Feb;58(2):467-74.
    doi: 10.1002/art.23302pubmed: 18240244google scholar: lookup
  20. Demoor M, Ollitrault D, Gomez-Leduc T, Bouyoucef M, Hervieu M, Fabre H, Lafont J, Denoix JM, Audigié F, Mallein-Gerin F, Legendre F, Galera P. Cartilage tissue engineering: molecular control of chondrocyte differentiation for proper cartilage matrix reconstruction.. Biochim Biophys Acta 2014 Aug;1840(8):2414-40.
    doi: 10.1016/j.bbagen.2014.02.030pubmed: 24608030google scholar: lookup
  21. Huang BJ, Huey DJ, Hu JC, Athanasiou KA. Engineering biomechanically functional neocartilage derived from expanded articular chondrocytes through the manipulation of cell-seeding density and dexamethasone concentration.. J Tissue Eng Regen Med 2017 Aug;11(8):2323-2332.
    doi: 10.1002/term.2132pubmed: 27138113google scholar: lookup
  22. Vinatier C, Mrugala D, Jorgensen C, Guicheux J, Noël D. Cartilage engineering: a crucial combination of cells, biomaterials and biofactors.. Trends Biotechnol 2009 May;27(5):307-14.
    doi: 10.1016/j.tibtech.2009.02.005pubmed: 19329205google scholar: lookup
  23. Duval E, Leclercq S, Elissalde JM, Demoor M, Galéra P, Boumédiene K. Hypoxia-inducible factor 1alpha inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia-inducible factor 1alpha-dependent redifferentiation of chondrocytes.. Arthritis Rheum 2009 Oct;60(10):3038-48.
    pubmed: 19790048doi: 10.1002/art.24851google scholar: lookup
  24. Lee HH, Chang CC, Shieh MJ, Wang JP, Chen YT, Young TH, Hung SC. Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K/Akt/FoxO dependent anti-apoptotic effect.. Sci Rep 2013;3:2683.
    doi: 10.1038/srep02683pmc: PMC3775095pubmed: 24042188google scholar: lookup
  25. Lafont JE, Poujade FA, Pasdeloup M, Neyret P, Mallein-Gerin F. Hypoxia potentiates the BMP-2 driven COL2A1 stimulation in human articular chondrocytes via p38 MAPK.. Osteoarthritis Cartilage 2016 May;24(5):856-67.
    doi: 10.1016/j.joca.2015.11.017pubmed: 26708156google scholar: lookup
  26. Hautier A, Salentey V, Aubert-Foucher E, Bougault C, Beauchef G, Ronzière MC, De Sobarnitsky S, Paumier A, Galéra P, Piperno M, Damour O, Mallein-Gerin F. Bone morphogenetic protein-2 stimulates chondrogenic expression in human nasal chondrocytes expanded in vitro.. Growth Factors 2008 Aug;26(4):201-11.
    doi: 10.1080/08977190802242488pubmed: 18720162google scholar: lookup
  27. Claus S, Aubert-Foucher E, Demoor M, Camuzeaux B, Paumier A, Piperno M, Damour O, Duterque-Coquillaud M, Galéra P, Mallein-Gerin F. Chronic exposure of bone morphogenetic protein-2 favors chondrogenic expression in human articular chondrocytes amplified in monolayer cultures.. J Cell Biochem 2010 Dec 15;111(6):1642-51.
    doi: 10.1002/jcb.22897pubmed: 21053273google scholar: lookup
  28. Jiménez G, López-Ruiz E, Kwiatkowski W, Montañez E, Arrebola F, Carrillo E, Gray PC, Izpisua Belmonte JC, Choe S, Perán M, Marchal JA. Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes.. Sci Rep 2015 Nov 13;5:16400.
    doi: 10.1038/srep16400pmc: PMC4643338pubmed: 26563344google scholar: lookup
  29. Ollitrault D, Legendre F, Drougard C, Briand M, Benateau H, Goux D, Chajra H, Poulain L, Hartmann D, Vivien D, Shridhar V, Baldi A, Mallein-Gerin F, Boumediene K, Demoor M, Galera P. BMP-2, hypoxia, and COL1A1/HtrA1 siRNAs favor neo-cartilage hyaline matrix formation in chondrocytes.. Tissue Eng Part C Methods 2015 Feb;21(2):133-47.
    doi: 10.1089/ten.tec.2013.0724pmc: PMC4313417pubmed: 24957638google scholar: lookup
  30. Launay S, Maubert E, Lebeurrier N, Tennstaedt A, Campioni M, Docagne F, Gabriel C, Dauphinot L, Potier MC, Ehrmann M, Baldi A, Vivien D. HtrA1-dependent proteolysis of TGF-beta controls both neuronal maturation and developmental survival.. Cell Death Differ 2008 Sep;15(9):1408-16.
    doi: 10.1038/cdd.2008.82pubmed: 18551132google scholar: lookup
  31. Graham JR, Chamberland A, Lin Q, Li XJ, Dai D, Zeng W, Ryan MS, Rivera-Bermúdez MA, Flannery CR, Yang Z. Serine protease HTRA1 antagonizes transforming growth factor-β signaling by cleaving its receptors and loss of HTRA1 in vivo enhances bone formation.. PLoS One 2013;8(9):e74094.
    doi: 10.1371/journal.pone.0074094pmc: PMC3770692pubmed: 24040176google scholar: lookup
  32. Oka C, Tsujimoto R, Kajikawa M, Koshiba-Takeuchi K, Ina J, Yano M, Tsuchiya A, Ueta Y, Soma A, Kanda H, Matsumoto M, Kawaichi M. HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins.. Development 2004 Mar;131(5):1041-53.
    doi: 10.1242/dev.00999pubmed: 14973287google scholar: lookup
  33. Tiaden AN, Breiden M, Mirsaidi A, Weber FA, Bahrenberg G, Glanz S, Cinelli P, Ehrmann M, Richards PJ. Human serine protease HTRA1 positively regulates osteogenesis of human bone marrow-derived mesenchymal stem cells and mineralization of differentiating bone-forming cells through the modulation of extracellular matrix protein.. Stem Cells 2012 Oct;30(10):2271-82.
    doi: 10.1002/stem.1190pubmed: 22865667google scholar: lookup
  34. Tiaden AN, Bahrenberg G, Mirsaidi A, Glanz S, Blüher M, Richards PJ. Novel Function of Serine Protease HTRA1 in Inhibiting Adipogenic Differentiation of Human Mesenchymal Stem Cells via MAP Kinase-Mediated MMP Upregulation.. Stem Cells 2016 Jun;34(6):1601-14.
    doi: 10.1002/stem.2297pubmed: 26864869google scholar: lookup
  35. Grau S, Richards PJ, Kerr B, Hughes C, Caterson B, Williams AS, Junker U, Jones SA, Clausen T, Ehrmann M. The role of human HtrA1 in arthritic disease.. J Biol Chem 2006 Mar 10;281(10):6124-9.
    doi: 10.1074/jbc.M500361200pubmed: 16377621google scholar: lookup
  36. Polur I, Lee PL, Servais JM, Xu L, Li Y. Role of HTRA1, a serine protease, in the progression of articular cartilage degeneration.. Histol Histopathol 2010 May;25(5):599-608.
    pmc: PMC2894561pubmed: 20238298doi: 10.14670/hh-25.599google scholar: lookup
  37. Vonk LA, Kragten AH, Dhert WJ, Saris DB, Creemers LB. Overexpression of hsa-miR-148a promotes cartilage production and inhibits cartilage degradation by osteoarthritic chondrocytes.. Osteoarthritis Cartilage 2014 Jan;22(1):145-53.
    doi: 10.1016/j.joca.2013.11.006pubmed: 24269634google scholar: lookup
  38. Zhou HW, Lou SQ, Zhang K. Recovery of function in osteoarthritic chondrocytes induced by p16INK4a-specific siRNA in vitro.. Rheumatology (Oxford) 2004 May;43(5):555-68.
    doi: 10.1093/rheumatology/keh127pubmed: 15026580google scholar: lookup
  39. Lianxu C, Hongti J, Changlong Y. NF-kappaBp65-specific siRNA inhibits expression of genes of COX-2, NOS-2 and MMP-9 in rat IL-1beta-induced and TNF-alpha-induced chondrocytes.. Osteoarthritis Cartilage 2006 Apr;14(4):367-76.
    doi: 10.1016/j.joca.2005.10.009pubmed: 16376111google scholar: lookup
  40. Galera P, Ollitrault D, Legendre F, Demoor M, Mallein-Gerin F, Boumediene K, Herbage B, Duterque-Coquillaud M, Damour O. Method for Obtaining Differentiated Articular Chondrocytes In Vitro or Ex Vivo, and Uses of Same. WO2012038668 A1. 2012 Mar 29.
  41. Fermor B, Christensen SE, Youn I, Cernanec JM, Davies CM, Weinberg JB. Oxygen, nitric oxide and articular cartilage.. Eur Cell Mater 2007 Apr 11;13:56-65; discussion 65.
    doi: 10.22203/eCM.v013a06pubmed: 17427142google scholar: lookup
  42. Clausen T, Southan C, Ehrmann M. The HtrA family of proteases: implications for protein composition and cell fate.. Mol Cell 2002 Sep;10(3):443-55.
    doi: 10.1016/S1097-2765(02)00658-5pubmed: 12408815google scholar: lookup
  43. Ringe J, Burmester GR, Sittinger M. Regenerative medicine in rheumatic disease-progress in tissue engineering.. Nat Rev Rheumatol 2012 Aug;8(8):493-8.
    doi: 10.1038/nrrheum.2012.98pubmed: 22782007google scholar: lookup
  44. Gómez-Leduc T, Hervieu M, Legendre F, Bouyoucef M, Gruchy N, Poulain L, de Vienne C, Herlicoviez M, Demoor M, Galéra P. Chondrogenic commitment of human umbilical cord blood-derived mesenchymal stem cells in collagen matrices for cartilage engineering.. Sci Rep 2016 Sep 8;6:32786.
    doi: 10.1038/srep32786pmc: PMC5015060pubmed: 27604951google scholar: lookup
  45. Legendre F, Ollitrault D, Hervieu M, Baugé C, Maneix L, Goux D, Chajra H, Mallein-Gerin F, Boumediene K, Galera P, Demoor M. Enhanced hyaline cartilage matrix synthesis in collagen sponge scaffolds by using siRNA to stabilize chondrocytes phenotype cultured with bone morphogenetic protein-2 under hypoxia.. Tissue Eng Part C Methods 2013 Jul;19(7):550-67.
    doi: 10.1089/ten.tec.2012.0508pubmed: 23270543google scholar: lookup
  46. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blöcker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, MacLeod JN, Penedo MC, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guérin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Røed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Lander ES, Lindblad-Toh K. Genome sequence, comparative analysis, and population genetics of the domestic horse.. Science 2009 Nov 6;326(5954):865-7.
    doi: 10.1126/science.1178158pmc: PMC3785132pubmed: 19892987google scholar: lookup
  47. Tran-Khanh N, Hoemann CD, McKee MD, Henderson JE, Buschmann MD. Aged bovine chondrocytes display a diminished capacity to produce a collagen-rich, mechanically functional cartilage extracellular matrix.. J Orthop Res 2005 Nov;23(6):1354-62.
    doi: 10.1016/j.orthres.2005.05.009.1100230617pubmed: 16048738google scholar: lookup
  48. Sumita Y, Honda MJ, Ohara T, Tsuchiya S, Sagara H, Kagami H, Ueda M. Performance of collagen sponge as a 3-D scaffold for tooth-tissue engineering.. Biomaterials 2006 Jun;27(17):3238-48.
    doi: 10.1016/j.biomaterials.2006.01.055pubmed: 16504285google scholar: lookup
  49. Nakase Y, Hagiwara A, Nakamura T, Kin S, Nakashima S, Yoshikawa T, Fukuda K, Kuriu Y, Miyagawa K, Sakakura C, Otsuji E, Shimizu Y, Ikada Y, Yamagishi H. Tissue engineering of small intestinal tissue using collagen sponge scaffolds seeded with smooth muscle cells.. Tissue Eng 2006 Feb;12(2):403-12.
    doi: 10.1089/ten.2006.12.403pubmed: 16548698google scholar: lookup
  50. Suzuki S, Kawai K, Ashoori F, Morimoto N, Nishimura Y, Ikada Y. Long-term follow-up study of artificial dermis composed of outer silicone layer and inner collagen sponge.. Br J Plast Surg 2000 Dec;53(8):659-66.
    doi: 10.1054/bjps.2000.3426pubmed: 11090321google scholar: lookup
  51. Russlies M, Behrens P, Wünsch L, Gille J, Ehlers EM. A cell-seeded biocomposite for cartilage repair.. Ann Anat 2002 Jul;184(4):317-23.
    doi: 10.1016/S0940-9602(02)80045-0pubmed: 12201040google scholar: lookup
  52. Cho YG, Cho ML, Min SY, Kim HY. Type II collagen autoimmunity in a mouse model of human rheumatoid arthritis.. Autoimmun Rev 2007 Nov;7(1):65-70.
    doi: 10.1016/j.autrev.2007.08.001pubmed: 17967728google scholar: lookup
  53. Lee K, Silva EA, Mooney DJ. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments.. J R Soc Interface 2011 Feb 6;8(55):153-70.
    doi: 10.1098/rsif.2010.0223pmc: PMC3033020pubmed: 20719768google scholar: lookup
  54. Pujol JP, Chadjichristos C, Legendre F, Bauge C, Beauchef G, Andriamanalijaona R, Galera P, Boumediene K. Interleukin-1 and transforming growth factor-beta 1 as crucial factors in osteoarthritic cartilage metabolism.. Connect Tissue Res 2008;49(3):293-7.
    doi: 10.1080/03008200802148355pubmed: 18661363google scholar: lookup
  55. Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS, Khvorova A. Rational siRNA design for RNA interference.. Nat Biotechnol 2004 Mar;22(3):326-30.
    doi: 10.1038/nbt936pubmed: 14758366google scholar: lookup
  56. Shao Y, Chan CY, Maliyekkel A, Lawrence CE, Roninson IB, Ding Y. Effect of target secondary structure on RNAi efficiency.. RNA 2007 Oct;13(10):1631-40.
    doi: 10.1261/rna.546207pmc: PMC1986803pubmed: 17684233google scholar: lookup
  57. Lorenz R, Bernhart SH, Höner Zu Siederdissen C, Tafer H, Flamm C, Stadler PF, Hofacker IL. ViennaRNA Package 2.0.. Algorithms Mol Biol 2011 Nov 24;6:26.
    doi: 10.1186/1748-7188-6-26pmc: PMC3319429pubmed: 22115189google scholar: lookup
  58. Gotkin MG, Ripley CR, Lamande SR, Bateman JF, Bienkowski RS. Intracellular trafficking and degradation of unassociated proalpha2 chains of collagen type I.. Exp Cell Res 2004 Jun 10;296(2):307-16.
    doi: 10.1016/j.yexcr.2004.01.029pubmed: 15149860google scholar: lookup
  59. Saxena S, Jónsson ZO, Dutta A. Small RNAs with imperfect match to endogenous mRNA repress translation. Implications for off-target activity of small inhibitory RNA in mammalian cells.. J Biol Chem 2003 Nov 7;278(45):44312-9.
    doi: 10.1074/jbc.M307089200pubmed: 12952966google scholar: lookup
  60. Xu L, Golshirazian I, Asbury BJ, Li Y. Induction of high temperature requirement A1, a serine protease, by TGF-beta1 in articular chondrocytes of mouse models of OA.. Histol Histopathol 2014 May;29(5):609-18.
    pubmed: 24135912doi: 10.14670/hh-29.10.609google scholar: lookup
  61. Wu X, Chim SM, Kuek V, Lim BS, Chow ST, Zhao J, Yang S, Rosen V, Tickner J, Xu J. HtrA1 is upregulated during RANKL-induced osteoclastogenesis, and negatively regulates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK and p38 phosphorylation.. FEBS Lett 2014 Jan 3;588(1):143-50.
    doi: 10.1016/j.febslet.2013.11.022pubmed: 24269886google scholar: lookup
  62. Branly T, Bertoni L, Contentin R, Rakic R, Gomez-Leduc T, Desancé M, Hervieu M, Legendre F, Jacquet S, Audigié F, Denoix JM, Demoor M, Galéra P. Characterization and use of Equine Bone Marrow Mesenchymal Stem Cells in Equine Cartilage Engineering. Study of their Hyaline Cartilage Forming Potential when Cultured under Hypoxia within a Biomaterial in the Presence of BMP-2 and TGF-ß1.. Stem Cell Rev Rep 2017 Oct;13(5):611-630.
    doi: 10.1007/s12015-017-9748-ypubmed: 28597211google scholar: lookup
  63. Schmidt EE, Pelz O, Buhlmann S, Kerr G, Horn T, Boutros M. GenomeRNAi: a database for cell-based and in vivo RNAi phenotypes, 2013 update.. Nucleic Acids Res 2013 Jan;41(Database issue):D1021-6.
    doi: 10.1093/nar/gks1170pmc: PMC3531141pubmed: 23193271google scholar: lookup
  64. Tang W, Dodge M, Gundapaneni D, Michnoff C, Roth M, Lum L. A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer.. Proc Natl Acad Sci U S A 2008 Jul 15;105(28):9697-702.
    doi: 10.1073/pnas.0804709105pmc: PMC2453074pubmed: 18621708google scholar: lookup
  65. Day TF, Guo X, Garrett-Beal L, Yang Y. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis.. Dev Cell 2005 May;8(5):739-50.
    doi: 10.1016/j.devcel.2005.03.016pubmed: 15866164google scholar: lookup
  66. Tuan RS. Cellular signaling in developmental chondrogenesis: N-cadherin, Wnts, and BMP-2.. J Bone Joint Surg Am 2003;85-A Suppl 2:137-41.
    doi: 10.2106/00004623-200300002-00019pubmed: 12721357google scholar: lookup
  67. Clynes M. In: Basic Cell Culture—A Practical Approach. Davis J.M., editor. IRL Press at Oxford University Press; Oxford, UK: 1996. p. 301.
  68. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method.. Nat Protoc 2008;3(6):1101-8.
    doi: 10.1038/nprot.2008.73pubmed: 18546601google scholar: lookup

Citations

This article has been cited 18 times.
  1. Cullier A, Cassé F, Manivong S, Contentin R, Legendre F, Garcia Ac A, Sirois P, Roullin G, Banquy X, Moldovan F, Bertoni L, Audigié F, Galéra P, Demoor M. Functionalized Nanogels with Endothelin-1 and Bradykinin Receptor Antagonist Peptides Decrease Inflammatory and Cartilage Degradation Markers of Osteoarthritis in a Horse Organoid Model of Cartilage. Int J Mol Sci 2022 Aug 11;23(16).
    doi: 10.3390/ijms23168949pubmed: 36012214google scholar: lookup
  2. Liu X, Zhang Z, Shi Y, Meng X, Qiu Z, Qu X, Dang J, Zhang Y, Sun L, Wang L, Zhu D, Mi Z, He J, Fan H. Effect of electrohydrodynamic printing scaffold with different spacing on chondrocyte dedifferentiation. Ann Transl Med 2022 Jul;10(13):743.
    doi: 10.21037/atm-22-2796pubmed: 35957706google scholar: lookup
  3. Contentin R, Jammes M, Bourdon B, Cassé F, Bianchi A, Audigié F, Branly T, Velot É, Galéra P. Bone Marrow MSC Secretome Increases Equine Articular Chondrocyte Collagen Accumulation and Their Migratory Capacities. Int J Mol Sci 2022 May 21;23(10).
    doi: 10.3390/ijms23105795pubmed: 35628604google scholar: lookup
  4. Liu W, Madry H, Cucchiarini M. Application of Alginate Hydrogels for Next-Generation Articular Cartilage Regeneration. Int J Mol Sci 2022 Jan 20;23(3).
    doi: 10.3390/ijms23031147pubmed: 35163071google scholar: lookup
  5. Hu X, Zhang W, Li X, Zhong D, Li Y, Li J, Jin R. Strategies to Modulate the Redifferentiation of Chondrocytes. Front Bioeng Biotechnol 2021;9:764193.
    doi: 10.3389/fbioe.2021.764193pubmed: 34881234google scholar: lookup
  6. Bourdon B, Contentin R, Cassé F, Maspimby C, Oddoux S, Noël A, Legendre F, Gruchy N, Galéra P. Marine Collagen Hydrolysates Downregulate the Synthesis of Pro-Catabolic and Pro-Inflammatory Markers of Osteoarthritis and Favor Collagen Production and Metabolic Activity in Equine Articular Chondrocyte Organoids. Int J Mol Sci 2021 Jan 8;22(2).
    doi: 10.3390/ijms22020580pubmed: 33430111google scholar: lookup
  7. Yuan ZD, Zhu WN, Liu KZ, Huang ZP, Han YC. Small Molecule Epigenetic Modulators in Pure Chemical Cell Fate Conversion. Stem Cells Int 2020;2020:8890917.
    doi: 10.1155/2020/8890917pubmed: 33144865google scholar: lookup
  8. Chen Y, Wu B, Lin J, Yu D, Du X, Sheng Z, Yu Y, An C, Zhang X, Li Q, Zhu S, Sun H, Zhang X, Zhang S, Zhou J, Bunpetch V, El-Hashash A, Ji J, Ouyang H. High-Resolution Dissection of Chemical Reprogramming from Mouse Embryonic Fibroblasts into Fibrocartilaginous Cells. Stem Cell Reports 2020 Mar 10;14(3):478-492.
    doi: 10.1016/j.stemcr.2020.01.013pubmed: 32084387google scholar: lookup
  9. Rakic R, Bourdon B, Demoor M, Maddens S, Saulnier N, Galéra P. Differences in the intrinsic chondrogenic potential of equine umbilical cord matrix and cord blood mesenchymal stromal/stem cells for cartilage regeneration. Sci Rep 2018 Sep 14;8(1):13799.
    doi: 10.1038/s41598-018-28164-9pubmed: 30217993google scholar: lookup
  10. Medvedeva EV, Grebenik EA, Gornostaeva SN, Telpuhov VI, Lychagin AV, Timashev PS, Chagin AS. Repair of Damaged Articular Cartilage: Current Approaches and Future Directions. Int J Mol Sci 2018 Aug 11;19(8).
    doi: 10.3390/ijms19082366pubmed: 30103493google scholar: lookup
  11. Contentin R, Jehl C, Commenchail K, Legendre F, Galéra P, Cassé F, Demoor M. Mechanical Stimulation of Equine Bone Marrow Mesenchymal Stromal Cell-Derived Cartilage-Like In Vitro Model Triggers Osteoarthritis Features. ACS Biomater Sci Eng 2025 Jul 14;11(7):4153-4165.
    doi: 10.1021/acsbiomaterials.5c00500pubmed: 40512481google scholar: lookup
  12. Chen B, Liu X, Hu M, Liao J. Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk. J Orthop Translat 2025 May;52:419-440.
    doi: 10.1016/j.jot.2025.03.005pubmed: 40485850google scholar: lookup
  13. Tong H, Guo X, Chen L, Wang H, Hu X, He A, Li C, Zhang T, Kang J, Fu Y. Quercetin prevents the loss of chondrogenic capacity in expansion cultured human auricular chondrocytes by alleviating mitochondrial dysfunction. Regen Ther 2025 Mar;28:358-370.
    doi: 10.1016/j.reth.2025.01.005pubmed: 39896443google scholar: lookup
  14. Wu X, Fu Y, Ma J, Li C, He A, Zhang T. LGR5 Modulates Differentiated Phenotypes of Chondrocytes Through PI3K/AKT Signaling Pathway. Tissue Eng Regen Med 2024 Jul;21(5):791-807.
    doi: 10.1007/s13770-024-00645-1pubmed: 38771465google scholar: lookup
  15. Yao Y, Chen K, Pan Q, Gao H, Su W, Zheng S, Dong W, Qian D. Redifferentiation of genetically modified dedifferentiated chondrocytes in a microcavitary hydrogel. Biotechnol Lett 2024 Jun;46(3):483-495.
    doi: 10.1007/s10529-024-03475-2pubmed: 38523201google scholar: lookup
  16. Sun J, Chen W, Zhou Z, Chen X, Zuo Y, He J, Liu H. Tanshinone IIA Facilitates Efficient Cartilage Regeneration under Inflammatory Factors Caused Stress via Upregulating LncRNA NEAT1_2. Biomedicines 2023 Dec 12;11(12).
    doi: 10.3390/biomedicines11123291pubmed: 38137512google scholar: lookup
  17. Jammes M, Cassé F, Velot E, Bianchi A, Audigié F, Contentin R, Galéra P. Pro-Inflammatory Cytokine Priming and Purification Method Modulate the Impact of Exosomes Derived from Equine Bone Marrow Mesenchymal Stromal Cells on Equine Articular Chondrocytes. Int J Mol Sci 2023 Sep 16;24(18).
    doi: 10.3390/ijms241814169pubmed: 37762473google scholar: lookup
  18. Jammes M, Contentin R, Audigié F, Cassé F, Galéra P. Effect of pro-inflammatory cytokine priming and storage temperature of the mesenchymal stromal cell (MSC) secretome on equine articular chondrocytes. Front Bioeng Biotechnol 2023;11:1204737.
    doi: 10.3389/fbioe.2023.1204737pubmed: 37720315google scholar: lookup
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