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Article

Deletion of p21 expression accelerates cartilage tissue repair via chondrocyte proliferation

  • Authors:
    • Kazuyuki Ibaraki
    • Shinya Hayashi
    • Noriyuki Kanzaki
    • Shingo Hashimoto
    • Shinsuke Kihara
    • Masahiko Haneda
    • Kazuhiro Takeuchi
    • Takahiro Niikura
    • Ryosuke Kuroda
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
  • Pages: 2236-2242
    |
    Published online on: March 13, 2020
       https://doi.org/10.3892/mmr.2020.11028
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Abstract

Articular cartilage tissue has a poor healing potential, and when subjected to traumatic damage this tissue undergoes cartilage degeneration and osteoarthritis. The association between the regulation of cell cycle checkpoints and tissue regeneration has been previously investigated, and p21 was initially identified as a potent inhibitor of cell cycle progression. However, the effects of p21 defects on damaged tissue remain controversial. Therefore, the aim of the present study was to evaluate the effects of p21 deficiency on cartilage repair. A mouse model of articular cartilage repair was generated by inducing a patellar groove scratch in 8‑week‑old p21‑knockout (KO) mice and C57Bl/6 wild‑type (WT) mice. Mice were sacrificed at 4 and 8 weeks post‑surgery. The present study also investigated the effect of p21 deficiency on cartilage differentiation in ATDC5 cells in vitro. Safranin O staining results indicated that cartilage repair initially occurred in p21 KO mice. In addition, immunohistochemical analysis demonstrated that p21 KO upregulated proliferating cell nuclear antigen and increased cell proliferation. However, type II collagen and Sox9 expression levels remained unchanged in p21 KO and WT mice. Moreover, it was identified that p21 downregulation did not affect Sox9 and type II collagen expression levels in vitro. Furthermore, p21 deficiency promoted healing of articular cartilage damage, which was associated with cell proliferation in vivo, and increased chondrocyte proliferation but not differentiation in vitro. Therefore, the present results suggested that p21 does not affect Sox9 or type II collagen expression levels during cartilage differentiation in the repair of cartilage defects.
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1 

Rai MF and Sandell LJ: Regeneration of articular cartilage in healer and non-healer mice. Matrix Biol. 39:50–55. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Buckwalter JA, Rosenberg LC and Huniker EB: Articular cartilage: composition, structure, response to injury, and methods of facilitating repair. Articular Cartilage and Knee Joint Function: Basic Science and Arthroscopy. Ewing JW: Raven Press Ltd.; New York, NY: 1990

3 

Fitzgerald J, Rich C, Burkhardt D, Allen J, Herzka AS and Little CB: Evidence for articular cartilage regeneration in MRL/MpJ mice. Osteoarthritis Cartilage. 16:1319–1326. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Eltawil NM, De Bari C, Achan P, Pitzalis C and Dell'accio F: A novel in vivo murine model of cartilage regeneration. Age and strain-dependent outcome after joint surface injury. Osteoarthritis Cartilage. 17:695–704. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Bedelbaeva K, Snyder A, Gourevitch D, Clark L, Zhang XM, Leferovich J, Cheverud JM, Lieberman P and Heber-Katz E: Lack of p21 expression links cell cycle control and appendage regeneration in mice. Proc Natl Acad Sci USA. 107:5845–5850. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Arthur LM and Heber-Katz E: The role of p21 in regulating mammalian regeneration. Stem Cell Res Ther. 2:302011. View Article : Google Scholar : PubMed/NCBI

7 

Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ: The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 75:805–816. 1993. View Article : Google Scholar : PubMed/NCBI

8 

Suzuki A, Tsutomi Y, Akahane K, Araki T and Miura M: Resistance to Fas-mediated apoptosis: Activation of caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP. Oncogene. 17:931–939. 1998. View Article : Google Scholar : PubMed/NCBI

9 

Hayashi S, Fujishiro T, Hashimoto S, Kanzaki N, Chinzei N, Kihara S, Takayama K, Matsumoto T, Nishida K, Kurosaka M, et al: p21 deficiency is susceptible to osteoarthritis through STAT3 phosphorylation. Arthritis Res Ther. 17:3142015. View Article : Google Scholar : PubMed/NCBI

10 

Seoane J, Le HV and Massagué J: Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature. 419:729–734. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Kondo S, Nakagawa Y, Mizuno M, Katagiri K, Tsuji K, Kiuchi S, Ono H, Muneta T, Koga H and Sekiya I: Transplantation of aggregates of autologous synovial mesenchymal stem cells for treatment of cartilage defects in the femoral condyle and the femoral groove in microminipigs. Am J Sports Med. 47:2338–2347. 2019. View Article : Google Scholar : PubMed/NCBI

12 

Qasim M, Chae DS and Lee NY: Bioengineering strategies for bone and cartilage tissue regeneration using growth factors and stem cells. J Biomed Mater Res A. 108:394–411. 2020. View Article : Google Scholar : PubMed/NCBI

13 

Nakagawa Y, Fortier LA, Mao JJ, Lee CH, Goodale MB, Koff MF, Uppstrom TJ, Croen B, Wada S, Carballo CB, et al: Long-term evaluation of meniscal tissue formation in 3-dimensional-printed scaffolds with sequential release of connective tissue growth factor and TGF-β3 in an ovine model. Am J Sports Med. 47:2596–2607. 2019. View Article : Google Scholar : PubMed/NCBI

14 

Premnath P, Jorgenson B, Hess R, Tailor P, Louie D, Taiani J, Boyd S and Krawetz R: p21-/- mice exhibit enhanced bone regeneration after injury. BMC Musculoskelet Disord. 18:4352017. View Article : Google Scholar : PubMed/NCBI

15 

Kihara S, et al: Cyclin-dependent kinase inhibitor-1-deficient mice are susceptible to osteoarthritis associated with enhanced inflammation. JMBR. 32:991–1001. 2017.

16 

Matsuoka M, Onodera T, Sasazawa F, Momma D, Baba R, Hontani K and Iwasaki N: An articular cartilage repair model in common C57Bl/6 Mice. Tissue Eng Part C Methods. 21:767–772. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI and Goldberg VM: Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am. 76:579–592. 1994. View Article : Google Scholar : PubMed/NCBI

18 

Shukunami C, Shigeno C, Atsumi T, Ishizeki K, Suzuki F and Hiraki Y: Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: Differentiation-dependent gene expression of parathyroid hormone (PTH)/PTH-related peptide receptor. J Cell Biol. 133:457–468. 1996. View Article : Google Scholar : PubMed/NCBI

19 

Shukunami C, Ishizeki K, Atsumi T, Ohta Y, Suzuki F and Hiraki Y: Cellular hypertrophy and calcification of embryonal carcinoma-derived chondrogenic cell line ATDC5 in vitro. J Bone Miner Res. 12:1174–1188. 1997. View Article : Google Scholar : PubMed/NCBI

20 

Atsumi T, Miwa Y, Kimata K and Ikawa Y: A chondrogenic cell line derived from a differentiating culture of AT805 teratocarcinoma cells. Cell Differ Dev. 30:109–116. 1990. View Article : Google Scholar : PubMed/NCBI

21 

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 : PubMed/NCBI

22 

Schönenberger F, Deutzmann A, Ferrando-May E and Merhof D: Discrimination of cell cycle phases in PCNA-immunolabeled cells. BMC Bioinformatics. 16:1802015. View Article : Google Scholar : PubMed/NCBI

23 

Bi W, Deng JM, Zhang Z, Behringer RR and de Crombrugghe B: Sox9 is required for cartilage formation. Nat Genet. 22:85–89. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Akiyama H, Chaboissier MC, Martin JF, Schedl A and de Crombrugghe B: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev. 16:2813–2828. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Ng LJ, Wheatley S, Muscat GE, Conway-Campbell J, Bowles J, Wright E, Bell DM, Tam PP, Cheah KS and Koopman P: SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev Biol. 183:108–121. 1997. View Article : Google Scholar : PubMed/NCBI

26 

Chinzei N, Hayashi S, Hashimoto S, Kanzaki N, Iwasa K, Sakata S, Kihara S, Fujishiro T, Kuroda R and Kurosaka M: Cyclin dependent kinase inhibitor p21 does not impact embryonic endochondral ossification in mice. Mol Med Rep. 11:1601–1608. 2015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ibaraki K, Hayashi S, Kanzaki N, Hashimoto S, Kihara S, Haneda M, Takeuchi K, Niikura T and Kuroda R: Deletion of p21 expression accelerates cartilage tissue repair via chondrocyte proliferation. Mol Med Rep 21: 2236-2242, 2020.
APA
Ibaraki, K., Hayashi, S., Kanzaki, N., Hashimoto, S., Kihara, S., Haneda, M. ... Kuroda, R. (2020). Deletion of p21 expression accelerates cartilage tissue repair via chondrocyte proliferation. Molecular Medicine Reports, 21, 2236-2242. https://doi.org/10.3892/mmr.2020.11028
MLA
Ibaraki, K., Hayashi, S., Kanzaki, N., Hashimoto, S., Kihara, S., Haneda, M., Takeuchi, K., Niikura, T., Kuroda, R."Deletion of p21 expression accelerates cartilage tissue repair via chondrocyte proliferation". Molecular Medicine Reports 21.5 (2020): 2236-2242.
Chicago
Ibaraki, K., Hayashi, S., Kanzaki, N., Hashimoto, S., Kihara, S., Haneda, M., Takeuchi, K., Niikura, T., Kuroda, R."Deletion of p21 expression accelerates cartilage tissue repair via chondrocyte proliferation". Molecular Medicine Reports 21, no. 5 (2020): 2236-2242. https://doi.org/10.3892/mmr.2020.11028
Copy and paste a formatted citation
x
Spandidos Publications style
Ibaraki K, Hayashi S, Kanzaki N, Hashimoto S, Kihara S, Haneda M, Takeuchi K, Niikura T and Kuroda R: Deletion of p21 expression accelerates cartilage tissue repair via chondrocyte proliferation. Mol Med Rep 21: 2236-2242, 2020.
APA
Ibaraki, K., Hayashi, S., Kanzaki, N., Hashimoto, S., Kihara, S., Haneda, M. ... Kuroda, R. (2020). Deletion of p21 expression accelerates cartilage tissue repair via chondrocyte proliferation. Molecular Medicine Reports, 21, 2236-2242. https://doi.org/10.3892/mmr.2020.11028
MLA
Ibaraki, K., Hayashi, S., Kanzaki, N., Hashimoto, S., Kihara, S., Haneda, M., Takeuchi, K., Niikura, T., Kuroda, R."Deletion of p21 expression accelerates cartilage tissue repair via chondrocyte proliferation". Molecular Medicine Reports 21.5 (2020): 2236-2242.
Chicago
Ibaraki, K., Hayashi, S., Kanzaki, N., Hashimoto, S., Kihara, S., Haneda, M., Takeuchi, K., Niikura, T., Kuroda, R."Deletion of p21 expression accelerates cartilage tissue repair via chondrocyte proliferation". Molecular Medicine Reports 21, no. 5 (2020): 2236-2242. https://doi.org/10.3892/mmr.2020.11028
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