Skip to main content
SpringerLink
Log in

Effect of JEZTC, a synthetic compound, on proliferation and phenotype maintenance of rabbit articular chondrocytes in vitro

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Antioxidant may provide anti-arthritic effect that contributes to resolution of inflammation. Gallic acid (GA) and its derivatives were reported to be effective in treatment of arthritis. But GA-suppressed cell proliferation may compromise its effect on chondro-protection. In this study, we synthesized sulfonamido-based gallate-JEZTC and investigated its effect on rabbit articular chondrocytes through examination of the cell proliferation, morphology, viability, glycosaminoglycan (GAG) synthesis, and cartilage-specific gene expression. Results showed that JEZTC could effectively promote chondrocyte growth and enhance secretion and synthesis of cartilage extracellular matrix (ECM) by upregulating expression levels of aggrecan, collagen II, and Sox9 genes. Expression of collagen I which marked chondrocyte dedifferentiation was effectively downregulated by JEZTC. In addition, hypertrophy that may lead to chondrocyte ossification could not be detected in JEZTC groups. The results indicated JEZTC can well preserve the phenotype of chondrocytes. Range of 2.344 to 9.375 μg/ml is the recommended dose of JEZTC, which showed increased cell proliferation. Especially, JEZTC of 4.688 μg/ml showed the best performance. This study might provide a basis for development of a novel agent for the treatment of symptomatic chondral and osteochondral lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
Figure 8.
Figure 9.

Similar content being viewed by others

References

  • Adcocks C, Collin P, Buttle DJ (2002) Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglycan and type II collagen degradation in vitro. J Nutr 132:341–346

    CAS  PubMed  Google Scholar 

  • Akiyama H (2011) Transcriptional regulation in chondrogenesis by Sox9. Clin Calcium 21:845–851

    CAS  PubMed  Google Scholar 

  • Andriamanalijaona R, Kypriotou M, Baugé C, Renard E, Legendre F, Raoudi M, Boumediene K, Gatto H, Monginoux P, Pujol JP (2005) Comparative effects of 2 antioxidants, selenomethionine and epigallocatechin-gallate, on catabolic and anabolic gene expression of articular chondrocytes. J Rheumatol 32:1958–1967

    CAS  PubMed  Google Scholar 

  • Ash H, Nevo Z, Aviezer D (2001) Characteristics of cartilage biopsies used for autologous chondrocytes transplantation. Cell Transplant 10:203–208

    PubMed  Google Scholar 

  • Benya PD, Shaffer JD (1982) Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30:215–224

    Article  CAS  PubMed  Google Scholar 

  • Bi W, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B (1999) Sox9 is required for cartilage formation. Nat Genet 22:85–89

    Article  CAS  PubMed  Google Scholar 

  • Buschmann MD, Grodzinsky AJ (1995) A molecular model of proteoglycan-associated electrostatic forces in cartilage mechanics. J Biomech Eng 117:179–192

    Article  CAS  PubMed  Google Scholar 

  • Daschner F (1976) Inhibition of cell wall synthesis by sulfonamides and trimethoprim. Chemotherapy 22:12–18

    Article  CAS  PubMed  Google Scholar 

  • Davies SR, Chang LW, Patra D, Xing X, Posey K, Hecht J, Stormo GD, Sandell LJ (2007) Computational identification and functional validation of regulatory motifs in cartilage-expressed genes. Genome Res 17:1438–1447

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Farndale RW, Buttle DJ, Barrett AJ (1986) Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 883:173–177

    Article  CAS  PubMed  Google Scholar 

  • Goldring SR, Goldring MB (2004) The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res (427 Suppl):S27–36.

  • Karlsen TA, Shahdadfar A, Brinchmann JE (2010) Human primary articular chondrocytes, chondroblasts-like cells, and dedifferentiated chondrocytes: differences in gene, microRNA, and protein expression and phenotype. Tissue Eng Part C Methods 17:219–227

    Article  PubMed  Google Scholar 

  • Kim YJ, Sah RL, Doong JY, Grodzinsky AJ (1988) Fluorometric assay of DNA in cartilage explants using Hoechst 33258. Anal Biochem 174:168–176

    Article  CAS  PubMed  Google Scholar 

  • Kroes BH, van den Berg AJ, Quarles van Ufford HC, van Dijk H, Labadie RP (1992) Anti-inflammatory activity of gallic acid. Planta Med 58:499–504

    Article  CAS  PubMed  Google Scholar 

  • Kwan KM, Pang MK, Zhou S, Cowan SK, Kong RY, Pfordte T, Olsen BR, Sillence DO, Tam PP, Cheah KS (1997) Abnormal compartmentalization of cartilage matrix components in mice lacking collagen X: implications for function. J Cell Biol 136:459–471

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lu Z, Nie G, Belton PS, Tang H, Zhao B (2006) Structure–activity relationship analysis of antioxidant ability and neuroprotective effect of gallic acid derivatives. Neurochem Int 48:263–274

    Article  CAS  PubMed  Google Scholar 

  • Marshall OJ, Harley VR (2000) Molecular mechanisms of SOX9 action. Mol Genet Metab 71:455–462

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Nuti E, Santamaria S, Casalini F, Yamamoto K, Marinelli L, La Pietra V, Novellino E, Orlandini E, Nencetti S, Marini AM, Salerno S, Taliani S, Da Settimo F, Nagase H, Rossello A (2013) Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: synthesis and biological evaluation. Eur J Med Chem 62:379–394

    Article  CAS  PubMed  Google Scholar 

  • Ou TT, Lin MC, Wu CH, Lin WL, Wang CJ (2013) Gallic acid attenuates oleic acid-induced proliferation of vascular smooth muscle cell through regulation of AMPK-eNOS-FAS signaling. Curr Med Chem 20:3944–3953

    Article  CAS  PubMed  Google Scholar 

  • Patoux-Pibouin M, Hirel B, Chesne C, Watier E, Chevrant-Breton J, Guillouzo A (1995) Cytotoxicity testing of beta-lactam antibiotics, non-steroidal anti-inflammatory drugs and sulfonamides in primary human keratinocyte cultures. Toxicol in Vitro 9:493–497

    Article  CAS  PubMed  Google Scholar 

  • Paul R, Haydon RC, Cheng H, Ishikawa A, Nenadovich N, Jiang W, Zhou L, Breyer B, Feng T, Gupta P, He TC, Phillips FM (2003) Potential use of Sox9 gene therapy for intervertebral degenerative disc disease. Spine 28:755–763

    PubMed Central  PubMed  Google Scholar 

  • Ramprasath VR, Shanthi P, Sachdanandam P (2005) Evaluation of antioxidant effect of Semecarpus anacardium Linn. nut extract on the components of immune system in adjuvant arthritis. Vasc Pharmacol 42:179–186

    Article  CAS  Google Scholar 

  • Schnabel M, Marlovits S, Eckhoff G, Fichtel I, Gotzen L, Vécsei V, Schlegel J (2002) Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthr Cartil 10:62–70

    Article  CAS  PubMed  Google Scholar 

  • Schulze-Tanzil G (2009) Activation and dedifferentiation of chondrocytes: implications in cartilage injury and repair. Ann Anat 191:325–338

    Article  CAS  PubMed  Google Scholar 

  • Tew SR, Clegg PD (2011) Analysis of post transcriptional regulation of SOX9 mRNA during in vitro chondrogenesis. Tissue Eng A 17:1801–1807

    Article  CAS  Google Scholar 

  • Tew SR, Li Y, Pothacharoen P, Tweats LM, Hawkins RE, Hardingham TE (2005) Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes. Osteoarthr Cartil 13:80–89

    Article  PubMed  Google Scholar 

  • Tsuchiya H, Kitoh H, Sugiura F, Ishiguro N (2003) Chondrogenesis enhanced by overexpression of Sox9 gene in mouse bone marrow-derived mesenchymal stem cells. Biochem Biophys Res Commun 301:338–343

    Article  CAS  PubMed  Google Scholar 

  • Vankemmelbeke MN, Jones GC, Fowles C, Ilic MZ, Handley CJ, Day AJ, Knight CG, Mort JS, Buttle DJ (2003) Selective inhibition of ADAMTS −1, −4 and −5 by catechin gallate esters. Eur J Biochem 270:2394–2403

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Cha YN, Kim KS, Kim C (2011) Taurine chloramine inhibits osteoclastogenesis and splenic lymphocyte proliferation in mice with collagen-induced arthritis. Eur J Pharmacol 668:325–330

    Article  CAS  PubMed  Google Scholar 

  • Wegst-Uhrich SR, Navarro DA, Zimmerman L, Aga DS (2014) Assessing antibiotic sorption in soil: a literature review and new case studies on sulfonamides and macrolides. Chem Cent J 17:8–5

    Google Scholar 

  • Yoon CH, Chung SJ, Lee SW, Park YB, Lee SK, Park MC (2013) Gallic acid, a natural polyphenolic acid, induces apoptosis and inhibits proinflammatory gene expressions in rheumatoid arthritis fibroblast-like synoviocytes. Joint Bone Spine 80:274–279

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work has been financially supported by the National Science & Technology Pillar Program of China (Grant No. 2012BAI42G00), National Natural Science Foundation of China (Grant No. 81260277), Guangxi Scientific Research and Technology Development Projects (Guikehe 14125008-2-14) and Open Project of Guangxi Key Laboratory of Quality Research in Chinese Medicines (Grant No. 201304).

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Osteopathy Ward, The First Affiliated Hospital, Research Center for Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China

    Lei Liu

  2. Research Center for Regenerative Medicine, The Medical and Scientific Research Center, Guangxi Medical University, Nanning, 530021, China

    Qin Liu, Qing Jun Wei & Li Zheng

  3. School of Chemistry and Chemical Engineering, Guangxi University, Nanning, 530004, Guangxi, China

    Xiao Lin

  4. Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning, 530022, China

    Xiao Lin

Authors
  1. Lei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing Jun Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Li Zheng.

Additional information

Editor: T. Okamoto

Q. Liu and X. Lin contributed equally to this paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, L., Liu, Q., Lin, X. et al. Effect of JEZTC, a synthetic compound, on proliferation and phenotype maintenance of rabbit articular chondrocytes in vitro. In Vitro Cell.Dev.Biol.-Animal 50, 982–991 (2014). https://doi.org/10.1007/s11626-014-9795-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-014-9795-5

Keywords

Search

Navigation