Stem cells and development2013; 22(8); 1288-1296; doi: 10.1089/scd.2012.0411

MicroRNA-140 expression during chondrogenic differentiation of equine cord blood-derived mesenchymal stromal cells.

Abstract: MicroRNAs are a class of short noncoding RNAs that are involved in various biological processes, including differentiation. MicroRNA-140 (miR-140) has been identified as a cartilage-specific microRNA with several targets involved in cartilage development and homeostasis. The aim of this study was to investigate the expression of miR-140 during chondrogenic differentiation of equine cord blood-derived mesenchymal stromal cells (eCB-MSCs). We demonstrate both that miR-140 is highly expressed in normal equine articular cartilage and that eCB-MSCs express significantly higher levels of this microRNA after 14 days of chondrogenic differentiation. Furthermore, miR-140 expression closely paralleled that of the cartilage-specific transcription factor Sox9, suggesting that miR-140 may be under the transcriptional regulation of Sox9 in these cells. The expression patterns of miR-140 targets the chemokine (CXC motif) ligand 12 (CXCL12), A disintegrin and metalloproteinase with thrombosponin motifs (ADAMTS)-5 and insulin growth factor binding protein 5 (IGFBP5) were also determined; however, only CXCL12 and ADAMTS-5 were repressed while miR-140 expression was upregulated. Together, these studies suggest that miR-140 is an important regulator of cartilage development and homeostasis in eCB-MSCs that may act, in part, through the regulation of CXCL12 and ADAMTS-5.
Publication Date: 2013-01-15 PubMed ID: 23157248DOI: 10.1089/scd.2012.0411Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article describes an investigation into the role of MicroRNA-140 (miR-140) during the chondrogenic (cartilage forming) differentiation of equine cord blood-derived mesenchymal stromal cells (eCB-MSCs). The study found that miR-140, a cartilage-specific microRNA, is highly expressed in normal equine articular cartilage and its expression rises significantly in eCB-MSCs after two weeks of chondrogenic differentiation.

About MicroRNAs

  • MicroRNAs are a class of short noncoding RNAs — i.e., sequences of RNA that do not code for proteins. They’re involved in a range of biological processes, including cellular differentiation — the process in which unspecialized cells mature into their specialized forms.
  • MicroRNA-140, in particular, is noted as a cartilage-specific microRNA. This means it plays a major role in the development and maintenance (homeostasis) of cartilage.

The Study and Its Findings

  • The study’s goal was to explore how miR-140 behaves during the chondrogenic differentiation of eCB-MSCs — essentially, when these cells were made to develop into cartilage cells.
  • The researchers found that miR-140 is present in high quantities in healthy equine articular cartilage (the cartilage found in joints).
  • More importantly, when they induced chondrogenic differentiation in eCB-MSCs, the cells showed significantly increased levels of miR-140 expression after 14 days. This finding suggests a crucial role for miR-140 in cartilage formation.
  • The researchers also found that miR-140’s expression pattern closely matched that of Sox9, a transcription factor known to be specific to cartilage. This finding suggests that Sox9 may control miR-140’s expression in these cells.

Regulation of miR-140 Targets

  • Additionally, the researchers examined how the miR-140 expression pattern affected the expression of its various targets, such as chemokine CXCL12, ADAMTS-5, and IGFBP5. These targets have roles in cartilage development and homeostasis.
  • While all three targets were expected to be downregulated (repressed) with the upregulation of miR-140, only CXCL12 and ADAMTS-5 behaved as expected, suggesting miR-140 regulates these targets during chondrogenic differentiation.

Implications of the Study

  • Together, these results propose that miR-140 plays a significant role in the development and maintenance of cartilage in eCB-MSCs. The discovery furthers our understanding of cartilage growth and could potentially assist in devising effective therapies for diseases that involve cartilage degradation, like osteoarthritis.

Cite This Article

APA
Buechli ME, Lamarre J, Koch TG. (2013). MicroRNA-140 expression during chondrogenic differentiation of equine cord blood-derived mesenchymal stromal cells. Stem Cells Dev, 22(8), 1288-1296. https://doi.org/10.1089/scd.2012.0411

Publication

ISSN: 1557-8534
NlmUniqueID: 101197107
Country: United States
Language: English
Volume: 22
Issue: 8
Pages: 1288-1296

Researcher Affiliations

Buechli, Midori E
  • Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Lamarre, Jonathan
    Koch, Thomas G

      MeSH Terms

      • ADAM Proteins / genetics
      • ADAM Proteins / metabolism
      • Aggrecans / genetics
      • Aggrecans / metabolism
      • Animals
      • Cartilage, Articular / cytology
      • Cell Differentiation / genetics
      • Cells, Cultured
      • Chemokine CXCL12 / genetics
      • Chemokine CXCL12 / metabolism
      • Chondrocytes / cytology
      • Chondrocytes / metabolism
      • Chondrogenesis / genetics
      • Collagen / genetics
      • Collagen / metabolism
      • Fetal Blood / cytology
      • Gene Expression
      • Horses
      • Immunohistochemistry
      • Insulin-Like Growth Factor Binding Protein 5 / genetics
      • Insulin-Like Growth Factor Binding Protein 5 / metabolism
      • Mesenchymal Stem Cells / cytology
      • Mesenchymal Stem Cells / metabolism
      • MicroRNAs / genetics
      • Reverse Transcriptase Polymerase Chain Reaction
      • SOX9 Transcription Factor / genetics
      • SOX9 Transcription Factor / metabolism
      • Time Factors

      Citations

      This article has been cited 18 times.
      1. Hu WS, Zhang Q, Li SH, Ai SC, Wu QF. Ten Hotspot MicroRNAs and Their Potential Targets of Chondrocytes Were Revealed in Osteoarthritis Based on Bibliometric Analysis.. J Healthc Eng 2022;2022:8229148.
        doi: 10.1155/2022/8229148pubmed: 35437466google scholar: lookup
      2. Li D, Gupta P, Sgaglione NA, Grande DA. Exosomes Derived from Non-Classic Sources for Treatment of Post-Traumatic Osteoarthritis and Cartilage Injury of the Knee: In Vivo Review.. J Clin Med 2021 May 7;10(9).
        doi: 10.3390/jcm10092001pubmed: 34066986google scholar: lookup
      3. Antunes J, Lee O, Alizadeh AH, LaMarre J, Koch TG. Why the hype - What are microRNAs and why do they provide unique investigative, diagnostic, and therapeutic opportunities in veterinary medicine?. Can Vet J 2020 Aug;61(8):845-852.
        pubmed: 32741990
      4. Budd E, Waddell S, de Andru00e9s MC, Oreffo ROC. The Potential of microRNAs for Stem Cell-based Therapy for Degenerative Skeletal Diseases.. Curr Mol Biol Rep 2017;3(4):263-275.
        doi: 10.1007/s40610-017-0076-4pubmed: 29214143google scholar: lookup
      5. Yin CM, Suen WC, Lin S, Wu XM, Li G, Pan XH. Dysregulation of both miR-140-3p and miR-140-5p in synovial fluid correlate with osteoarthritis severity.. Bone Joint Res 2017 Nov;6(11):612-618.
      6. Tao SC, Yuan T, Zhang YL, Yin WJ, Guo SC, Zhang CQ. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model.. Theranostics 2017;7(1):180-195.
        doi: 10.7150/thno.17133pubmed: 28042326google scholar: lookup
      7. Unger L, Fouchu00e9 N, Leeb T, Gerber V, Pacholewska A. Optimized methods for extracting circulating small RNAs from long-term stored equine samples.. Acta Vet Scand 2016 Jun 29;58(1):44.
        doi: 10.1186/s13028-016-0224-5pubmed: 27356979google scholar: lookup
      8. Lee S, Hwang S, Yu HJ, Oh D, Choi YJ, Kim MC, Kim Y, Ryu DY. Expression of microRNAs in Horse Plasma and Their Characteristic Nucleotide Composition.. PLoS One 2016;11(1):e0146374.
        doi: 10.1371/journal.pone.0146374pubmed: 26731407google scholar: lookup
      9. Russell KA, Gibson TW, Chong A, Co C, Koch TG. Canine Platelet Lysate Is Inferior to Fetal Bovine Serum for the Isolation and Propagation of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells.. PLoS One 2015;10(9):e0136621.
        doi: 10.1371/journal.pone.0136621pubmed: 26353112google scholar: lookup
      10. Chen S, Fu P, Cong R, Wu H, Pei M. Strategies to minimize hypertrophy in cartilage engineering and regeneration.. Genes Dis 2015 Mar 1;2(1):76-95.
        doi: 10.1016/j.gendis.2014.12.003pubmed: 26000333google scholar: lookup
      11. Gu00fcllu00fc G, Peker I, Haholu A, Eren F, Ku00fcu00e7u00fckodaci Z, Gu00fcleu00e7 B, Baloglu H, Erzik C, u00d6zer A, Akkiprik M. Clinical significance of miR-140-5p and miR-193b expression in patients with breast cancer and relationship to IGFBP5.. Genet Mol Biol 2015 Mar;38(1):21-9.
        doi: 10.1590/S1415-475738120140167pubmed: 25983620google scholar: lookup
      12. Guo F, Wang Y, Liu J, Mok SC, Xue F, Zhang W. CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks.. Oncogene 2016 Feb 18;35(7):816-26.
        doi: 10.1038/onc.2015.139pubmed: 25961926google scholar: lookup
      13. Yang Z, Hao J, Hu ZM. MicroRNA expression profiles in human adipose-derived stem cells during chondrogenic differentiation.. Int J Mol Med 2015 Mar;35(3):579-86.
        doi: 10.3892/ijmm.2014.2051pubmed: 25543998google scholar: lookup
      14. Jingsheng S, Yibing W, Jun X, Siqun W, Jianguo W, Feiyan C, Gangyong H, Jie C. MicroRNAs are potential prognostic and therapeutic targets in diabetic osteoarthritis.. J Bone Miner Metab 2015 Jan;33(1):1-8.
        doi: 10.1007/s00774-014-0628-0pubmed: 25245120google scholar: lookup
      15. Gurusinghe S, Strappe P. Gene modification of mesenchymal stem cells and articular chondrocytes to enhance chondrogenesis.. Biomed Res Int 2014;2014:369528.
        doi: 10.1155/2014/369528pubmed: 24963479google scholar: lookup
      16. Pievani A, Scagliotti V, Russo FM, Azario I, Rambaldi B, Sacchetti B, Marzorati S, Erba E, Giudici G, Riminucci M, Biondi A, Vergani P, Serafini M. Comparative analysis of multilineage properties of mesenchymal stromal cells derived from fetal sources shows an advantage of mesenchymal stromal cells isolated from cord blood in chondrogenic differentiation potential.. Cytotherapy 2014 Jul;16(7):893-905.
        doi: 10.1016/j.jcyt.2014.02.008pubmed: 24794181google scholar: lookup
      17. Li J, Ohliger J, Pei M. Significance of epigenetic landscape in cartilage regeneration from the cartilage development and pathology perspective.. Stem Cells Dev 2014 Jun 1;23(11):1178-94.
        doi: 10.1089/scd.2014.0002pubmed: 24555773google scholar: lookup
      18. Barter MJ, Young DA. Epigenetic mechanisms and non-coding RNAs in osteoarthritis.. Curr Rheumatol Rep 2013 Sep;15(9):353.
        doi: 10.1007/s11926-013-0353-zpubmed: 23888362google scholar: lookup