Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
November-2018 Volume 42 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2018 Volume 42 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2

  • Authors:
    • Jiaqing Cao
    • Xinyou Han
    • Xin Qi
    • Xiangyun Jin
    • Xiaolin Li
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China
    Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2560-2568
    |
    Published online on: August 7, 2018
       https://doi.org/10.3892/ijmm.2018.3811
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

One of the hallmarks of osteoarthritis (OA) development is endochondral ossification, in which Runt‑related transcription factor‑2 (Runx2) is aberrantly expressed. Runx2 was previously identified to be regulated by microRNA‑204‑5p (miR‑204‑5p). The aim of the present study was to investigate the potential function of miR‑204‑5p regulating Runx2 during the development of OA and the underlying molecular mechanism. The expression levels of miR‑204‑5p and Runx2 were determined in tissue specimens. Rat OA models were established by transecting the anterior and posterior cruciate ligaments and removing the meniscus. Rats were treated with miR‑204‑5p agomir and miR‑204‑5p negative control (NC). All in vitro experiments were performed using rat primary chondrocytes and the SW‑1353 human bone chondrosarcoma cell line. It was identified that the expression of miR‑204‑5p was significantly decreased, whereas Runx2 was significantly increased, in human OA tissues compared with in non‑OA tissues, and levels were inversely associated with each other in primary chondrocytes and chondrosarcoma cells. Overexpression of miR‑204‑5p decreased the proliferation of chondrocytes and SW‑1353 cells. Using a luciferase reporter assay, Runx2 was identified to be a direct target of miR‑204‑5p in chondrocytes and overexpressed miR‑204‑5p altered the expression of collagens II, X and matrix metalloproteinase (MMP)‑1 and MMP‑13 in primary chondrocytes and SW‑1353 cells. Histological analysis revealed that miR‑204‑5p treatment ameliorated the OA‑like phenotype that is reflected by assessment of cartilage thickness and Mankin's score. Runx2 expression was gradually increased as the rats increased in age. At 10 weeks of miR‑204‑5p agomir treatment, altered expression levels of collagens II and X, cartilage oligomeric matrix protein fragment, aggrecan, MMP‑1 and MMP‑13 were observed in the treatment group compared with the NC group. In conclusion, the results of the present study indicated that miR‑204‑5p decreases chondrocyte proliferation and ameliorates the OA‑like phenotype in rats with surgically induced OA by targeting Runx2.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Kim HA, Lee YJ, Seong SC, Choe KW and Song YW: Apoptotic chondrocyte death in human osteoarthritis. J Rheumatol. 27:455–462. 2000.PubMed/NCBI

2 

Dreier R: Hypertrophic differentiation of chondrocytes in osteoarthritis: The developmental aspect of degenerative joint disorders. Arthritis Res Ther. 12:2162010. View Article : Google Scholar : PubMed/NCBI

3 

Chen H, Ghori-Javed FY, Rashid H, Adhami MD, Serra R, Gutierrez SE and Javed A: Runx2 regulates endochondral ossification through control of chondrocyte proliferation and differentiation. J Bone Miner Res. 29:2653–2665. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Yoshida CA, Yamamoto H, Fujita T, Furuichi T, Ito K, Inoue K, Yamana K, Zanma A, Takada K, Ito Y and Komori T: Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev. 18:952–963. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Xu Ji Q, Xu X, Fan Y, Kang Z, Li L, Liang L, Guo Y, Hong J, Li TZ, et al: miR-105/Runx2 axis mediates FGF2-induced ADAMTS expression in osteoarthritis cartilage. J Mol Med. 94:681–694. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Altorok N, Tsou PS, Coit P, Khanna D and Sawalha AH: Genome-wide DNA methylation analysis in dermal fibroblasts from patients with diffuse and limited systemic sclerosis reveals common and subset-specific DNA methylation aberrancies. Ann Rheum Dis. 74:1612–1620. 2015. View Article : Google Scholar

7 

Guo F, Han X, Wu Z, Cheng Z, Hu Q, Zhao Y, Wang Y and Liu C: ATF6a, a Runx2-activable transcription factor, is a new regulator of chondrocyte hypertrophy. J Cell Sci. 129:717–728. 2016. View Article : Google Scholar

8 

Yates LA, Norbury CJ and Gilbert RJ: The long and short of microRNA. Cell. 153:516–519. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Le LT, Swingler TE and Clark IM: Review: The role of microRNAs in osteoarthritis and chondrogenesis. Arthritis Rheum. 65:1963–1974. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Yu C, Li L, Xie F, Guo S, Liu F, Dong N and Wang Y: LncRNA TUG1 sponges miR-204 5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification. Cardiovasc Res. 114:168–179. 2018. View Article : Google Scholar

11 

Shang G, Wang Y, Xu Y, Zhang S, Sun X, Guan H, Zhao X, Wang Y, Li Y and Zhao G: Long non-coding RNA TCONS_00041960 enhances osteogenesis and inhibits adipogenesis of rat bone marrow mesenchymal stem cell by targeting miR-204-5p and miR-125a-3p. J Cell Physiol. 233:6041–6051. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Huang J, Zhao L, Xing L and Chen D: MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 28:357–364. 2010.

13 

Zhang Y, Xie RL, Croce CM, Stein JL, Lian JB, van Wijnen AJ and Stein GS: A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2. Proc Natl Acad Sci USA. 108:9863–9868. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Belaya Z, Grebennikova T, Melnichenko G, Nikitin A, Solodovnikov A, Brovkina O, Grigoriev A, Rozhinskaya L, Lutsenko A and Dedov I: Effects of active acromegaly on bone mRNA and microRNA expression patterns. Eur J Endocrinol. 178:353–364. 2018. View Article : Google Scholar : PubMed/NCBI

15 

Rogart JN, Barrach HJ and Chichester CO: Articular collagen degradation in the Hulth-Telhag model of osteoarthritis. Osteoarthritis Cartilage. 7:539–547. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Chen L, Li Q, Wang J, Jin S, Zheng H, Lin J, He F, Zhang H, Ma S, Mei J and Yu J: MiR-29b 3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN. J Cell Mol Med. 21:3347–3359. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Jin Y, Chen Z, Liu X and Zhou X: Evaluating the microRNA targeting sites by luciferase reporter gene assay. Methods Mol Biol. 936:117–127. 2013. View Article : Google Scholar :

18 

Kuroki H, Nakagawa Y, Mori K, Ohba M, Suzuki T, Mizuno Y, Ando K, Takenaka M, Ikeuchi K and Nakamura T: Acoustic stiffness and change in plug cartilage over time after autologous osteochondral grafting: Correlation between ultrasound signal intensity and histological score in a rabbit model. Arthritis Res Ther. 6:R492–R504. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Bulstra SK, Buurman WA, Walenkamp GH and Van der Linden AJ: Metabolic characteristics of in vitro cultured human chondrocytes in relation to the histopathologic grade of osteoarthritis. Clin Orthop Relat Res. 294–302. 1989.PubMed/NCBI

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

21 

Lu J, Ji ML, Zhang XJ, Shi PL, Wu H, Wang C and Im HJ: MicroRNA-218 5p as a potential target for the treatment of human osteoarthritis. Mol Ther. 12:2676–2688. 2017. View Article : Google Scholar

22 

Balaskas P, Goljanek-Whysall K, Clegg P, Fang Y, Cremers A, Emans P, Welting T and Peffers M: MicroRNA profiling in cartilage ageing. Int J Genomics. 2017:27137252017. View Article : Google Scholar : PubMed/NCBI

23 

Hong BK, You S, Yoo SA, Park D, Hwang D, Cho CS and Kim WU: MicroRNA-143 and -145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis. Exp Mol Med. 49:e3632017. View Article : Google Scholar : PubMed/NCBI

24 

Sümbül AT, Göğebakan B, Ergün S, Yengil E, Batmacı CY, Tonyalı Ö and Yaldız M: miR-204 5p expression in colorectal cancer: An autophagy-associated gene. Tumour Biol. 35:12713–12719. 2014. View Article : Google Scholar

25 

Wu C, Tian B, Qu X, Liu F, Tang T, Qin A, Zhu Z and Dai K: MicroRNAs play a role in chondrogenesis and osteoarthritis (review). Int J Mol Med. 34:13–23. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Wuelling M and Vortkamp A: Chondrocyte proliferation and differentiation. Endocr Dev. 21:1–11. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Hosaka Y, Saito T, Sugita S, Hikata T, Kobayashi H, Fukai A, Taniguchi Y, Hirata M, Akiyama H, Chung UI and Kawaguchi H: Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development. Proc Natl Acad Sci USA. 110:1875–1880. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, et al: Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 89:755–764. 1997. View Article : Google Scholar : PubMed/NCBI

29 

Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, et al: Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. 89:765–771. 1997. View Article : Google Scholar : PubMed/NCBI

30 

Lee YJ, Park SY, Lee SJ, Boo YC, Choi JY and Kim JE: Ucma, a direct transcriptional target of Runx2 and Osterix, promotes osteoblast differentiation and nodule formation. Osteoarthritis Cartilage. 23:1421–1431. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Komori T: Regulation of skeletal development by the Runx family of transcription factors. J Cell Biochem. 95:445–453. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Hashimoto K, Oda Y, Nakamura F, Kakinoki R and Akagi M: Lectin-like, oxidized low-density lipoprotein receptor-1-deficient mice show resistance to age-related knee osteoarthritis. Eur J Histochem. 61:27622017. View Article : Google Scholar : PubMed/NCBI

33 

DeLise AM, Fischer L and Tuan RS: Cellular interactions and signaling in cartilage development. Osteoarthritis Cartilage. 8:309–334. 2000. View Article : Google Scholar : PubMed/NCBI

34 

Quarto R, Campanile G, Cancedda R and Dozin B: Modulation of commitment, proliferation, and differentiation of chondrogenic cells in defined culture medium. Endocrinology. 138:4966–4976. 1997. View Article : Google Scholar : PubMed/NCBI

35 

Goldring MB, Tsuchimochi K and Ijiri K: The control of chondrogenesis. J Cell Biochem. 97:33–44. 2006. View Article : Google Scholar

36 

Hesselstrand R, Kassner A, Heinegard D and Saxne T: COMP: A candidate molecule in the pathogenesis of systemic sclerosis with a potential as a disease marker. Ann Rheum Dis. 67:1242–1248. 2008. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cao J, Han X, Qi X, Jin X and Li X: miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2. Int J Mol Med 42: 2560-2568, 2018.
APA
Cao, J., Han, X., Qi, X., Jin, X., & Li, X. (2018). miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2. International Journal of Molecular Medicine, 42, 2560-2568. https://doi.org/10.3892/ijmm.2018.3811
MLA
Cao, J., Han, X., Qi, X., Jin, X., Li, X."miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2". International Journal of Molecular Medicine 42.5 (2018): 2560-2568.
Chicago
Cao, J., Han, X., Qi, X., Jin, X., Li, X."miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2". International Journal of Molecular Medicine 42, no. 5 (2018): 2560-2568. https://doi.org/10.3892/ijmm.2018.3811
Copy and paste a formatted citation
x
Spandidos Publications style
Cao J, Han X, Qi X, Jin X and Li X: miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2. Int J Mol Med 42: 2560-2568, 2018.
APA
Cao, J., Han, X., Qi, X., Jin, X., & Li, X. (2018). miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2. International Journal of Molecular Medicine, 42, 2560-2568. https://doi.org/10.3892/ijmm.2018.3811
MLA
Cao, J., Han, X., Qi, X., Jin, X., Li, X."miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2". International Journal of Molecular Medicine 42.5 (2018): 2560-2568.
Chicago
Cao, J., Han, X., Qi, X., Jin, X., Li, X."miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2". International Journal of Molecular Medicine 42, no. 5 (2018): 2560-2568. https://doi.org/10.3892/ijmm.2018.3811
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team