Analyze Diet
Animals : an open access journal from MDPI2021; 11(9); 2542; doi: 10.3390/ani11092542

HOX Gene Expressions in Cultured Articular and Nasal Equine Chondrocytes.

Abstract: Osteoarthritis the quality and span of life in horses. Previous studies focused on nasal cartilage as a possible source for autologous chondrocyte implantation (ACI) in cartilage defects in humans. "HOX gene-negative" nasal chondrocytes adapted articular HOX patterns after implantation into caprine joint defects and produced cartilage matrix proteins. We compared the HOX gene profile of equine chondrocytes of nasal septum, anterior and posterior fetlock to identify nasal cartilage as a potential source for ACI in horses. Cartilage was harvested from seven horses after death and derived chondrocytes were cultured in a monolayer to fourth subcultivation. HOX A3, D1, D8 and chondrocyte markers COL2 and SOX9 were analyzed with qPCR in chondrocytes of three different locations obtained during passage 0 and passage 2. HOX gene expression showed no significant differences between the locations but varied significantly between the horses. HOX genes and SOX9 remained stable during culturing. Cultured nasal chondrocytes may be a target for future research in cell-based regenerative therapies in equine osteoarthritis. The involvement of HOX genes in the high regenerative and adaptive potential of nasal chondrocytes observed in previous studies could not be confirmed.
Publication Date: 2021-08-30 PubMed ID: 34573508PubMed Central: PMC8471089DOI: 10.3390/ani11092542Google 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.

The study investigates equine cartilage cells (chondrocytes) from different body parts to evaluate their potential use in cell-based regenerative therapies for horse osteoarthritis. The focus is on comparing cellular expressions of particular ‘HOX’ genes in articular (joint) and nasal (nose) cartilage cells.

Understanding the Objective

  • The purpose of this research is to determine whether nasal cartilage could be a viable source of cells for autologous chondrocyte implantation (ACI) in horses. ACI is a procedure where the chondrocytes are taken from the patient, grown in a lab, and then re-implanted into the patient to repair cartilage defects.
  • “HOX genes” are a group of related genes that control the body plan of an embryo along the head tail axis. In this study, the researchers were interested in these gene expressions in the cells of articular and nasal cartilage of horses, particularly looking at the genes HOX A3, D1, and D8.
  • The chondrocyte markers COL2 and SOX9 were also examined. These markers are used to identify the cellular origin and degree of differentiation of the cells. More specifically, COL2 is a major fibrous protein found in cartilage while SOX9 plays a role in the development of cartilage.

The Research Process

  • The researchers collected cartilage cells from the nasal septum and two individual regions of the fetlock (the joint between the cannon bone and the pastern) of seven horses post-mortem. The fourth round of subculture was used for the analysis, providing a good amount of cells to study.
  • They analyzed gene expression with quantitative PCR (qPCR), a technique that quantifies the amount of target DNA in a sample.

The Research Findings

  • There was no significant difference found in the expression of HOX genes between cells from the different locations within individual horses. However, the expressions varied significantly between different horses. In addition, the expression of HOX genes and SOX9 remained stable during the culture process.
  • Given these findings, cultured nasal chondrocytes carry potential for future research in cell-based regenerative therapies in equine osteoarthritis as the cells remained stable during culturing and may be a viable source for ACI.
  • The researchers were unable to confirm the involvement of HOX genes in the regenerative and adaptive potential of nasal chondrocytes, as seen in previous studies. More research is necessary to explore this in greater depth.

Cite This Article

APA
Storch C, Fuhrmann H, Schoeniger A. (2021). HOX Gene Expressions in Cultured Articular and Nasal Equine Chondrocytes. Animals (Basel), 11(9), 2542. https://doi.org/10.3390/ani11092542

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 11
Issue: 9
PII: 2542

Researcher Affiliations

Storch, Christiane
  • Institute of Biochemistry, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 1, 04103 Leipzig, Germany.
Fuhrmann, Herbert
  • Institute of Biochemistry, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 1, 04103 Leipzig, Germany.
Schoeniger, Axel
  • Institute of Biochemistry, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 1, 04103 Leipzig, Germany.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 51 references
  1. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. Repair and tissue engineering techniques for articular cartilage.. Nat Rev Rheumatol 2015 Jan;11(1):21-34.
    doi: 10.1038/nrrheum.2014.157pmc: PMC4629810pubmed: 25247412google scholar: lookup
  2. Honvo G, Lengelé L, Charles A, Reginster JY, Bruyère O. Role of Collagen Derivatives in Osteoarthritis and Cartilage Repair: A Systematic Scoping Review With Evidence Mapping.. Rheumatol Ther 2020 Dec;7(4):703-740.
    doi: 10.1007/s40744-020-00240-5pmc: PMC7695755pubmed: 33068290google scholar: lookup
  3. Desancé M, Contentin R, Bertoni L, Gomez-Leduc T, Branly T, Jacquet S, Betsch JM, Batho A, Legendre F, Audigié F, Galéra P, Demoor M. Chondrogenic Differentiation of Defined Equine Mesenchymal Stem Cells Derived from Umbilical Cord Blood for Use in Cartilage Repair Therapy.. Int J Mol Sci 2018 Feb 10;19(2).
    doi: 10.3390/ijms19020537pmc: PMC5855759pubmed: 29439436google scholar: lookup
  4. Fuggle NR, Cooper C, Oreffo ROC, Price AJ, Kaux JF, Maheu E, Cutolo M, Honvo G, Conaghan PG, Berenbaum F, Branco J, Brandi ML, Cortet B, Veronese N, Kurth AA, Matijevic R, Roth R, Pelletier JP, Martel-Pelletier J, Vlaskovska M, Thomas T, Lems WF, Al-Daghri N, Bruyère O, Rizzoli R, Kanis JA, Reginster JY. Alternative and complementary therapies in osteoarthritis and cartilage repair.. Aging Clin Exp Res 2020 Apr;32(4):547-560.
    doi: 10.1007/s40520-020-01515-1pmc: PMC7170824pubmed: 32170710google scholar: lookup
  5. Kaneps AJ, Hinchcliff KW, Geor RJ. Equine Sports Medicine and Surgery: Basic and Clinical Sciences of the Equine Athlete. 2nd ed. Saunders/Elsevier; Edinburgh, UK: 2014. p. 1299.
  6. Bourebaba L, Röcken M, Marycz K. Osteochondritis dissecans (OCD) in Horses - Molecular Background of its Pathogenesis and Perspectives for Progenitor Stem Cell Therapy.. Stem Cell Rev Rep 2019 Jun;15(3):374-390.
    doi: 10.1007/s12015-019-09875-6pmc: PMC6534522pubmed: 30796679google scholar: lookup
  7. Fugazzola MC, van Weeren PR. Surgical osteochondral defect repair in the horse-a matter of form or function?. Equine Vet J 2020 Jul;52(4):489-499.
    doi: 10.1111/evj.13231pmc: PMC7317185pubmed: 31958175google scholar: lookup
  8. Li T, Chen S, Pei M. Contribution of neural crest-derived stem cells and nasal chondrocytes to articular cartilage regeneration.. Cell Mol Life Sci 2020 Dec;77(23):4847-4859.
    doi: 10.1007/s00018-020-03567-ypubmed: 32504256google scholar: lookup
  9. Lo Monaco M, Merckx G, Ratajczak J, Gervois P, Hilkens P, Clegg P, Bronckaers A, Vandeweerd JM, Lambrichts I. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.. Stem Cells Int 2018;2018:9079538.
    doi: 10.1155/2018/9079538pmc: PMC5832141pubmed: 29535784google scholar: lookup
  10. Kubosch EJ, Heidt E, Bernstein A, Böttiger K, Schmal H. The trans-well coculture of human synovial mesenchymal stem cells with chondrocytes leads to self-organization, chondrogenic differentiation, and secretion of TGFβ.. Stem Cell Res Ther 2016 Apr 26;7(1):64.
    doi: 10.1186/s13287-016-0322-3pmc: PMC4845486pubmed: 27118471google scholar: lookup
  11. Pelttari K, Winter A, Steck E, Goetzke K, Hennig T, Ochs BG, Aigner T, Richter W. Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice.. Arthritis Rheum 2006 Oct;54(10):3254-66.
    doi: 10.1002/art.22136pubmed: 17009260google scholar: lookup
  12. Park YB, Ha CW, Rhim JH, Lee HJ. Stem Cell Therapy for Articular Cartilage Repair: Review of the Entity of Cell Populations Used and the Result of the Clinical Application of Each Entity.. Am J Sports Med 2018 Aug;46(10):2540-2552.
    doi: 10.1177/0363546517729152pubmed: 29023156google scholar: lookup
  13. Music E, Futrega K, Doran MR. Sheep as a model for evaluating mesenchymal stem/stromal cell (MSC)-based chondral defect repair.. Osteoarthritis Cartilage 2018 Jun;26(6):730-740.
    doi: 10.1016/j.joca.2018.03.006pubmed: 29580978google scholar: lookup
  14. Karuppal R. Current concepts in the articular cartilage repair and regeneration.. J Orthop 2017 Jun;14(2):A1-A3.
    doi: 10.1016/j.jor.2017.05.001pmc: PMC5440635pubmed: 28559648google scholar: lookup
  15. Niemeyer P, Porichis S, Steinwachs M, Erggelet C, Kreuz PC, Schmal H, Uhl M, Ghanem N, Südkamp NP, Salzmann G. Long-term outcomes after first-generation autologous chondrocyte implantation for cartilage defects of the knee.. Am J Sports Med 2014 Jan;42(1):150-7.
    doi: 10.1177/0363546513506593pubmed: 24145948google scholar: lookup
  16. Taïhi I, Nassif A, Isaac J, Fournier BP, Ferré F. Head to Knee: Cranial Neural Crest-Derived Cells as Promising Candidates for Human Cartilage Repair.. Stem Cells Int 2019;2019:9310318.
    doi: 10.1155/2019/9310318pmc: PMC6350557pubmed: 30766608google scholar: lookup
  17. Neuman MK, Briggs KK, Masuda K, Sah RL, Watson D. A compositional analysis of cadaveric human nasal septal cartilage.. Laryngoscope 2013 Sep;123(9):2120-4.
    doi: 10.1002/lary.23727pmc: PMC3775909pubmed: 23821477google scholar: lookup
  18. Soshnikova N. Hox genes regulation in vertebrates.. Dev Dyn 2014 Jan;243(1):49-58.
    doi: 10.1002/dvdy.24014pubmed: 23832853google scholar: lookup
  19. Pelttari K, Pippenger B, Mumme M, Feliciano S, Scotti C, Mainil-Varlet P, Procino A, von Rechenberg B, Schwamborn T, Jakob M, Cillo C, Barbero A, Martin I. Adult human neural crest-derived cells for articular cartilage repair.. Sci Transl Med 2014 Aug 27;6(251):251ra119.
    doi: 10.1126/scitranslmed.3009688pubmed: 25163479google scholar: lookup
  20. Pelttari K, Mumme M, Barbero A, Martin I. Nasal chondrocytes as a neural crest-derived cell source for regenerative medicine.. Curr Opin Biotechnol 2017 Oct;47:1-6.
    doi: 10.1016/j.copbio.2017.05.007pubmed: 28551498google scholar: lookup
  21. Pippenger BE, Ventura M, Pelttari K, Feliciano S, Jaquiery C, Scherberich A, Walboomers XF, Barbero A, Martin I. Bone-forming capacity of adult human nasal chondrocytes.. J Cell Mol Med 2015 Jun;19(6):1390-9.
    doi: 10.1111/jcmm.12526pmc: PMC4459852pubmed: 25689393google scholar: lookup
  22. Garcia-Fernàndez J. The genesis and evolution of homeobox gene clusters.. Nat Rev Genet 2005 Dec;6(12):881-92.
    doi: 10.1038/nrg1723pubmed: 16341069google scholar: lookup
  23. Barandun M, Iselin LD, Santini F, Pansini M, Scotti C, Baumhoer D, Bieri O, Studler U, Wirz D, Haug M, Jakob M, Schaefer DJ, Martin I, Barbero A. Generation and characterization of osteochondral grafts with human nasal chondrocytes.. J Orthop Res 2015 Aug;33(8):1111-9.
    doi: 10.1002/jor.22865pubmed: 25994595google scholar: lookup
  24. Gay MH, Mehrkens A, Rittmann M, Haug M, Barbero A, Martin I, Schaeren S. Nose to back: compatibility of nasal chondrocytes with environmental conditions mimicking a degenerated intervertebral disc.. Eur Cell Mater 2019 Mar 22;37:214-232.
    doi: 10.22203/eCM.v037a13pubmed: 30900738google scholar: lookup
  25. Lefebvre V, Dvir-Ginzberg M. SOX9 and the many facets of its regulation in the chondrocyte lineage.. Connect Tissue Res 2017 Jan;58(1):2-14.
  26. Tew SR, Li Y, Pothacharoen P, Tweats LM, Hawkins RE, Hardingham TE. Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes.. Osteoarthritis Cartilage 2005 Jan;13(1):80-9.
    doi: 10.1016/j.joca.2004.10.011pubmed: 15639641google scholar: lookup
  27. Azarpeykan S, Dittmer KE. Evaluation of housekeeping genes for quantitative gene expression analysis in the equine kidney.. J Equine Sci 2016;27(4):165-168.
    doi: 10.1294/jes.27.165pmc: PMC5155135pubmed: 27974876google scholar: lookup
  28. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments.. Clin Chem 2009 Apr;55(4):611-22.
    doi: 10.1373/clinchem.2008.112797pubmed: 19246619google scholar: lookup
  29. D’haene B, Hellemans J. The importance of quality control during qPCR data analysis. Int. Drug Disc. 2010;18:24.
  30. Hellemans J, Mortier G, De Paepe A, Speleman F, Vandesompele J. qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data.. Genome Biol 2007;8(2):R19.
    doi: 10.1186/gb-2007-8-2-r19pmc: PMC1852402pubmed: 17291332google scholar: lookup
  31. Field A. Discovering Statistics Using IBM SPSS Statistics. 5th ed. Sage; London, UK: 2020.
  32. Blanca MJ, Alarcón R, Arnau J, Bono R, Bendayan R. Non-normal data: Is ANOVA still a valid option?. Psicothema 2017 Nov;29(4):552-557.
    doi: 10.7334/psicothema2016.383pubmed: 29048317google scholar: lookup
  33. Keller D. E-Book-Multiple-Lineare-Regression-Mit-SPSSIBM. 2016.
  34. Rux DR, Wellik DM. Hox genes in the adult skeleton: Novel functions beyond embryonic development.. Dev Dyn 2017 Apr;246(4):310-317.
    doi: 10.1002/dvdy.24482pmc: PMC5508556pubmed: 28026082google scholar: lookup
  35. Smith J, Zyoud A, Allegrucci C. A Case of Identity: HOX Genes in Normal and Cancer Stem Cells.. Cancers (Basel) 2019 Apr 10;11(4).
    doi: 10.3390/cancers11040512pmc: PMC6521190pubmed: 30974862google scholar: lookup
  36. Pineault KM, Wellik DM. Hox genes and limb musculoskeletal development.. Curr Osteoporos Rep 2014 Dec;12(4):420-7.
    doi: 10.1007/s11914-014-0241-0pmc: PMC4216602pubmed: 25266923google scholar: lookup
  37. Lee YK, Uchida H, Smith H, Ito A, Sanchez T. The isolation and molecular characterization of cerebral microvessels.. Nat Protoc 2019 Nov;14(11):3059-3081.
    doi: 10.1038/s41596-019-0212-0pubmed: 31586162google scholar: lookup
  38. Fleige S, Pfaffl MW. RNA integrity and the effect on the real-time qRT-PCR performance.. Mol Aspects Med 2006 Apr-Jun;27(2-3):126-39.
    doi: 10.1016/j.mam.2005.12.003pubmed: 16469371google scholar: lookup
  39. Bian Y, Wei J, Zhao C, Li G. Natural Polyphenols Targeting Senescence: A Novel Prevention and Therapy Strategy for Cancer.. Int J Mol Sci 2020 Jan 20;21(2).
    doi: 10.3390/ijms21020684pmc: PMC7013714pubmed: 31968672google scholar: lookup
  40. Kang SW, Yoo SP, Kim BS. Effect of chondrocyte passage number on histological aspects of tissue-engineered cartilage.. Biomed Mater Eng 2007;17(5):269-76.
    pubmed: 17851169
  41. Liang L, Shen YY, Pan XW, Zhou TC, Yang C, Irwin DM, Zhang YP. Adaptive evolution of the Hox gene family for development in bats and dolphins.. PLoS One 2013;8(6):e65944.
  42. Turner DC, Gorski PP, Maasar MF, Seaborne RA, Baumert P, Brown AD, Kitchen MO, Erskine RM, Dos-Remedios I, Voisin S, Eynon N, Sultanov RI, Borisov OV, Larin AK, Semenova EA, Popov DV, Generozov EV, Stewart CE, Drust B, Owens DJ, Ahmetov II, Sharples AP. DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity.. Sci Rep 2020 Sep 21;10(1):15360.
    doi: 10.1038/s41598-020-72730-zpmc: PMC7506549pubmed: 32958812google scholar: lookup
  43. Daftary GS, Taylor HS. Endocrine regulation of HOX genes.. Endocr Rev 2006 Jun;27(4):331-55.
    doi: 10.1210/er.2005-0018pubmed: 16632680google scholar: lookup
  44. Schnorr B, Kressin M. Embryologie der Haustiere: Ein Kurzlehrbuch. 5th ed. Enke; Stuttgart, Germany: 2006.
  45. Pelttari K, Barbero A, Martin I. A potential role of homeobox transcription factors in osteoarthritis.. Ann Transl Med 2015 Oct;3(17):254.
  46. Ecke A, Lutter AH, Scholka J, Hansch A, Becker R, Anderer U. Tissue Specific Differentiation of Human Chondrocytes Depends on Cell Microenvironment and Serum Selection.. Cells 2019 Aug 19;8(8).
    doi: 10.3390/cells8080934pmc: PMC6721655pubmed: 31430976google scholar: lookup
  47. Akens MK, Hurtig MB. Influence of species and anatomical location on chondrocyte expansion.. BMC Musculoskelet Disord 2005 May 17;6:23.
    doi: 10.1186/1471-2474-6-23pmc: PMC1166560pubmed: 15904515google scholar: lookup
  48. Francioli SE, Martin I, Sie CP, Hagg R, Tommasini R, Candrian C, Heberer M, Barbero A. Growth factors for clinical-scale expansion of human articular chondrocytes: relevance for automated bioreactor systems.. Tissue Eng 2007 Jun;13(6):1227-34.
    doi: 10.1089/ten.2006.0342pubmed: 17518725google scholar: lookup
  49. Szojka AR, Marqueti RC, Li DX, Molter CW, Liang Y, Kunze M, Mulet-Sierra A, Jomha NM, Adesida AB. Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression.. J Tissue Eng 2021 Jan-Dec;12:2041731421990842.
    doi: 10.1177/2041731421990842pmc: PMC7874349pubmed: 33613959google scholar: lookup
  50. Fitzgerald JB, Jin M, Dean D, Wood DJ, Zheng MH, Grodzinsky AJ. Mechanical compression of cartilage explants induces multiple time-dependent gene expression patterns and involves intracellular calcium and cyclic AMP.. J Biol Chem 2004 May 7;279(19):19502-11.
    doi: 10.1074/jbc.M400437200pubmed: 14960571google scholar: lookup
  51. Klinder A, Kussauer S, Hiemer B, Wree A, Bader R, Jonitz-Heincke A. Influence of Conditioned Media on the Re-Differentiation Capacity of Human Chondrocytes in 3D Spheroid Cultures.. J Clin Med 2020 Aug 30;9(9).
    doi: 10.3390/jcm9092798pmc: PMC7564315pubmed: 32872610google scholar: lookup

Citations

This article has been cited 1 times.
  1. Shestakova VA, Smirnova EI, Rao L, Kolobaev IV, Atiakshin DA, Ignatyuk MA, Krasheninnikov ME, Ahmedov BG, Ivanov SA, Klabukov ID, Shegay PV, Kaprin AD, Baranovskii DS. Nasal Chondrocytes Intensively Invade and Repair Pathologically Altered Cartilage Through Intrinsic Genomic Mechanisms: A Narrative Review. Curr Rheumatol Rev 2026;22(1):60-73.