Skip to main content
SpringerLink
Log in

p-Coumaric Acid Attenuates IL-1β-Induced Inflammatory Responses and Cellular Senescence in Rat Chondrocytes

  • Original Article
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Osteoarthritis (OA) is a common chronic inflammatory joint disease characterized by cartilage degradation. p-Coumaric acid (PCA), a dietary phenolic compound, has exerted anti-inflammatory and anti-oxidative activities in various diseases. However, the effects of PCA on OA have not been reported. In the present study, we aimed to investigate the effects of PCA on interleukin-1β(IL-1β)-induced inflammatory responses and cellular senescence in rat chondrocytes. Our results revealed that PCA remarkably downregulated IL-1β-induced inflammatory factors such as COX2 and iNOS and cartilage-degrading enzymes like matrix metalloproteinases (MMP1, MMP3, and MMP13) and aggrecanases (ADAMTS4 and ADAMTS5) in chondrocytes. The IL-1β-induced degradation of cartilage matrix (collagen II and aggrecan) could also be suppressed by PCA. Besides, PCA treatment effectively inhibited the IL-1β-induced p16INK4a protein expression and SAβ-gal activities in vitro. Mechanism analysis showed that PCA suppressed IL-1β-induced activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) pathways. In vivo, we also found that PCA could alleviate the development of OA in a rat model. Altogether, our findings implicate that p-coumaric acid attenuates IL-1β-induced inflammatory responses and cellular senescence via inhibition of the MAPK and NF-κB signaling pathway in chondrocytes, and p-coumaric acid may be a promising candidate for the treatment of osteoarthritis.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Boehme, K.A., and B. Rolauffs. 2018. Onset and progression of human osteoarthritis-can growth factors, inflammatory cytokines, or differential miRNA expression concomitantly induce proliferation, ECM degradation, and inflammation in articular cartilage? International Journal of Molecular Sciences 19.

  2. Sahin, S., S.A. Tuncel, K. Salimi, E. Bilgic, P. Korkusuz, and F. Korkusuz. 2018. Advanced injectable alternatives for osteoarthritis. Advances in Experimental Medicine and Biology 1077: 183–196.

    Article  CAS  Google Scholar 

  3. Zhu, Z., J. Li, G. Ruan, G. Wang, C. Huang, and C. Ding. 2018. Investigational drugs for the treatment of osteoarthritis, an update on recent developments. Expert Opinion on Investigational Drugs 27: 881–900.

    Article  CAS  Google Scholar 

  4. Hunter, D.J., and S. Bierma-Zeinstra. 2019. Osteoarthritis. Lancet. 393: 1745–1759.

    Article  CAS  Google Scholar 

  5. Messina, O.D., M. Vidal Wilman, and L.F. Vidal Neira. 2019. Nutrition, osteoarthritis and cartilage metabolism. Aging Clinical and Experimental Research 31: 807–813.

    Article  Google Scholar 

  6. Zhang, W., W.B. Robertson, J. Zhao, W. Chen, and J. Xu. 2019. Emerging Trend in the Pharmacotherapy of Osteoarthritis. Front Endocrinol (Lausanne) 10: 431.

    Article  Google Scholar 

  7. Conaghan, P.G., A.D. Cook, J.A. Hamilton, and P.P. Tak. 2019. Therapeutic options for targeting inflammatory osteoarthritis pain. Nature Reviews Rheumatology 15: 355–363.

    Article  Google Scholar 

  8. McMillen, B.A. 1985. Comparative chronic effects of buspirone or neuroleptics on rat brain dopaminergic neurotransmission. Journal of Neural Transmission 64: 1–12.

    Article  CAS  Google Scholar 

  9. Poulet, B., and K.A. Staines. 2016. New developments in osteoarthritis and cartilage biology. Current Opinion in Pharmacology 28: 8–13.

    Article  CAS  Google Scholar 

  10. Wang, T., and C. He. 2018. Pro-inflammatory cytokines: the link between obesity and osteoarthritis. Cytokine & Growth Factor Reviews 44: 38–50.

    Article  Google Scholar 

  11. McCulloch, K., G.J. Litherland, and T.S. Rai. 2017. Cellular senescence in osteoarthritis pathology. Aging Cell 16: 210–218.

    Article  CAS  Google Scholar 

  12. Price, J.S., J.G. Waters, C. Darrah, C. Pennington, D.R. Edwards, S.T. Donell, and I.M. Clark. 2002. The role of chondrocyte senescence in osteoarthritis. Aging Cell 1: 57–65.

    Article  CAS  Google Scholar 

  13. Zhou, H.W., S.Q. Lou, and K. Zhang. 2004. Recovery of function in osteoarthritic chondrocytes induced by p16INK4a-specific siRNA in vitro. Rheumatology (Oxford) 43: 555–568.

    Article  CAS  Google Scholar 

  14. Cha, H., S. Lee, J.H. Lee, and J.W. Park. 2018. Protective effects of p-coumaric acid against acetaminophen-induced hepatotoxicity in mice. Food and Chemical Toxicology 121: 131–139.

    Article  CAS  Google Scholar 

  15. Pragasam, S.J., and M. Rasool. 2013. Dietary component p-coumaric acid suppresses monosodium urate crystal-induced inflammation in rats. Inflammation Research 62: 489–498.

    Article  CAS  Google Scholar 

  16. Kheiry, M., M. Dianat, M. Badavi, S.A. Mard, and V. Bayati. 2019. p-Coumaric acid attenuates lipopolysaccharide-induced lung inflammation in rats by scavenging ROS production: an in vivo and in vitro study. Inflammation. 42: 1939–1950.

    Article  CAS  Google Scholar 

  17. Neog, M.K., S. Joshua Pragasam, M. Krishnan, and M. Rasool. 2017. p-Coumaric acid, a dietary polyphenol ameliorates inflammation and curtails cartilage and bone erosion in the rheumatoid arthritis rat model. Biofactors. 43: 698–717.

    Article  CAS  Google Scholar 

  18. Cheng, W., J. Jing, Z. Wang, D. Wu, and Y. Huang. 2017. Chondroprotective effects of ginsenoside Rg1 in human osteoarthritis chondrocytes and a rat model of anterior cruciate ligament transection. Nutrients 9.

  19. Gerwin, N., A.M. Bendele, S. Glasson, and C.S. Carlson. 2010. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat. Osteoarthritis and Cartilage 18 (Suppl 3): S24–S34.

    Article  Google Scholar 

  20. Mabey, T., and S. Honsawek. 2015. Cytokines as biochemical markers for knee osteoarthritis. World Journal of Orthopedics 6: 95–105.

    Article  Google Scholar 

  21. Amin, A.R., M. Dave, M. Attur, and S.B. Abramson. 2000. COX-2, NO, and cartilage damage and repair. Current Rheumatology Reports 2: 447–453.

    Article  CAS  Google Scholar 

  22. Haseeb, A., and T.M. Haqqi. 2013. Immunopathogenesis of osteoarthritis. Clinical Immunology 146: 185–196.

    Article  CAS  Google Scholar 

  23. Fan, Z., B. Bau, H. Yang, S. Soeder, and T. Aigner. 2005. Freshly isolated osteoarthritic chondrocytes are catabolically more active than normal chondrocytes, but less responsive to catabolic stimulation with interleukin-1beta. Arthritis and Rheumatism 52: 136–143.

    Article  CAS  Google Scholar 

  24. Goldring, M.B., and S.R. Goldring. 2007. Osteoarthritis. Journal of Cellular Physiology 213: 626–634.

    Article  CAS  Google Scholar 

  25. Troeberg, L., and H. Nagase. 1824. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochimica et Biophysica Acta 2012: 133–145.

    Google Scholar 

  26. Meszaros, E., and C.J. Malemud. 2012. Prospects for treating osteoarthritis: enzyme-protein interactions regulating matrix metalloproteinase activity. Therapeutic Advances in Chronic Disease 3: 219–229.

    Article  Google Scholar 

  27. Jenei-Lanzl, Z., A. Meurer, and F. Zaucke. 2019. Interleukin-1beta signaling in osteoarthritis - chondrocytes in focus. Cellular Signalling 53: 212–223.

    Article  CAS  Google Scholar 

  28. Hou, A., P. Chen, H. Tang, H. Meng, X. Cheng, Y. Wang, Y. Zhang, and J. Peng. 2018. Cellular senescence in osteoarthritis and anti-aging strategies. Mechanisms of Ageing and Development 175: 83–87.

    Article  CAS  Google Scholar 

  29. Jeon, O.H., C. Kim, R.M. Laberge, M. Demaria, S. Rathod, A.P. Vasserot, J.W. Chung, D.H. Kim, Y. Poon, N. David, D.J. Baker, J.M. van Deursen, J. Campisi, and J.H. Elisseeff. 2017. Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nature Medicine 23: 775–781.

    Article  CAS  Google Scholar 

  30. Xu, M., E.W. Bradley, M.M. Weivoda, S.M. Hwang, T. Pirtskhalava, T. Decklever, G.L. Curran, M. Ogrodnik, D. Jurk, K.O. Johnson, V. Lowe, T. Tchkonia, J.J. Westendorf, et al. 2017. Transplanted senescent cells induce an osteoarthritis-like condition in mice. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 72: 780–785.

    Article  CAS  Google Scholar 

  31. Wu, Y., L. Chen, Y. Wang, W. Li, Y. Lin, D. Yu, L. Zhang, F. Li, and Z. Pan. 2015. Overexpression of Sirtuin 6 suppresses cellular senescence and NF-kappaB mediated inflammatory responses in osteoarthritis development. Scientific Reports 5: 17602.

    Article  CAS  Google Scholar 

  32. Saklatvala, J. 2007. Inflammatory signaling in cartilage: MAPK and NF-kappaB pathways in chondrocytes and the use of inhibitors for research into pathogenesis and therapy of osteoarthritis. Current Drug Targets 8: 305–313.

    Article  CAS  Google Scholar 

  33. Zhang, Y., T. Pizzute, and M. Pei. 2014. A review of crosstalk between MAPK and Wnt signals and its impact on cartilage regeneration. Cell and Tissue Research 358: 633–649.

    Article  CAS  Google Scholar 

  34. Sondergaard, B.C., N. Schultz, S.H. Madsen, A.C. Bay-Jensen, M. Kassem, and M.A. Karsdal. 2010. MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation--divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation. Osteoarthritis and Cartilage 18: 279–288.

    Article  Google Scholar 

  35. Saito, T., and S. Tanaka. 2017. Molecular mechanisms underlying osteoarthritis development: Notch and NF-kappaB. Arthritis Research & Therapy 19: 94.

    Article  Google Scholar 

  36. Rigoglou, S., and A.G. Papavassiliou. 2013. The NF-kappaB signalling pathway in osteoarthritis. The International Journal of Biochemistry & Cell Biology 45: 2580–2584.

    Article  CAS  Google Scholar 

Download references

Funding

This study was sponsored by the National Natural Science Foundation of China (Grant no.81772390) and the Fundamental Research Funds for the Central Universities (grant no. 2017KFYXJJ104).

Author information

Author notes

    Authors and Affiliations

    1. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095#, Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China

      Xiaojian Huang, Yang Xi, Bowei Ni, Xiangyu Chu, Rui Zhang & Hongbo You

    2. School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 1095#, Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China

      Yingqian You

    Authors
    1. Xiaojian Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Yingqian You
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yang Xi
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Bowei Ni
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Xiangyu Chu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Rui Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Hongbo You
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Hongbo You.

    Ethics declarations

    All experimental procedures were conducted in accordance with the guidelines approved by the Experimental Animal Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

    Conflict of interest

    The authors declare that they have no conflicts of interest.

    Additional information

    Publisher’s Note

    Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

    Xiaojian Huang and Yingqian You contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Huang, X., You, Y., Xi, Y. et al. p-Coumaric Acid Attenuates IL-1β-Induced Inflammatory Responses and Cellular Senescence in Rat Chondrocytes. Inflammation 43, 619–628 (2020). https://doi.org/10.1007/s10753-019-01142-7

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10753-019-01142-7

    KEY WORDS

    Search

    Navigation