Advertisement

Inflammation

, Volume 42, Issue 2, pp 628–636 | Cite as

CPEB1 Expression Correlates with Severity of Posttraumatic Ankle Osteoarthritis and Aggravates Catabolic Effect of IL-1β on Chondrocytes

  • Lei LiEmail author
  • Jiaping Lan
  • Yongjie Ye
  • Bo Yang
  • Xiaoyong Yang
  • Zhijun Cai
ORIGINAL ARTICLE
  • 68 Downloads

Abstract

Most cases of posttraumatic ankle osteoarthritis (PTAOA) represent a sequela of ankle fractures. The cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is an RNA binding protein that controls protein expression. Here, we report the previously unappreciated association of CPEB1 with PTAOA. We found that CPEB1 was upregulated in articular cartilage from patients with PTAOA. Additionally, its expression level positively correlated with disease severity. In human primary chondrocytes cultured in vitro, CPEB1 was upregulated when treated with pro-inflammatory cytokines, i.e., IL-1β and TNF-α, suggesting that the observed CPEB1 upregulation in articular cartilage of PTAOA patients may be attributed to local inflammatory milieu. Functionally, CPEB1 overexpression aggravated the catabolic effect of IL-1β on chondrocytes in vitro, and vice versa, its knockdown reduced this effect, together implying a detrimental role of CPEB1 involved in OA progression. In sum, our study identifies CPEB1 as a potential regulator of disease progression of PTAOA.

KEY WORDS

CPEB1 correlation posttraumatic ankle osteoarthritis chondrocyte IL-1β catabolism 

Abbreviations

PTAOA

Posttraumatic ankle osteoarthritis

CPEB1

Cytoplasmic polyadenylation element-binding protein 1

UTR

Untranslated region

MMPs

Matrix metalloproteinases

siRNA

Small interfering RNA

MEFs

Mouse embryo fibroblasts

Notes

Compliance with Ethical Standards

The study design and sampling procedure were approved by the Medical Ethical Committee of Suining Central Hospital. The informed consents were obtained from all patients who consulted our institution for ankle OA evaluation and underwent amputation.

References

  1. 1.
    Alexandrov, I.M., M. Ivshina, D.Y. Jung, R. Friedline, H.J. Ko, M. Xu, B. O'Sullivan-Murphy, et al. 2012. Cytoplasmic polyadenylation element binding protein deficiency stimulates PTEN and Stat3 mRNA translation and induces hepatic insulin resistance. PLoS Genetics 8 (1): e1002457.  https://doi.org/10.1371/journal.pgen.1002457.CrossRefGoogle Scholar
  2. 2.
    Berger-Sweeney, J., N.R. Zearfoss, and J.D. Richter. 2006. Reduced extinction of hippocampal-dependent memories in CPEB knockout mice. Learning & Memory 13 (1): 4–7.  https://doi.org/10.1101/lm.73706. CrossRefGoogle Scholar
  3. 3.
    Blaney Davidson, E.N., A.P. van Caam, E.L. Vitters, M.B. Bennink, E. Thijssen, W.B. van den Berg, M.I. Koenders, P.L. van Lent, F.A. van de Loo, and P.M. van der Kraan. 2015. TGF-beta is a potent inducer of nerve growth factor in articular cartilage via the ALK5-Smad2/3 pathway. Potential role in OA related pain? Osteoarthritis and Cartilage 23 (3): 478–486.  https://doi.org/10.1016/j.joca.2014.12.005.CrossRefGoogle Scholar
  4. 4.
    Burns, D.M., and J.D. Richter. 2008. CPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation. Genes & Development 22 (24): 3449–3460.  https://doi.org/10.1101/gad.1697808.CrossRefGoogle Scholar
  5. 5.
    Delco, M.L., E.D. Bonnevie, P.G. Alexander, R.S. Tuan, L.J. Bonassar, and L.A. Fortier. 2017. An in vivo large animal model to study impact-induced cartilage injury and the development of early posttraumatic ankle osteoarthritis. Osteoarthritis and Cartilage 25: S309–S310.  https://doi.org/10.1016/j.joca.2017.02.519.CrossRefGoogle Scholar
  6. 6.
    Ding, Xiaojie, Lijuan Qiu, Lijuan Zhang, Juemin Xi, Duo Li, Xinwei Huang, Yujiao Zhao, Xiaodang Wang, and Qiangming Sun. 2016. The role of semaphorin 4D as a potential biomarker for antiangiogenic therapy in colorectal cancer. Oncotargets & Therapy 9 (Issue 1): 1189.Google Scholar
  7. 7.
    Groisman, I., M. Ivshina, V. Marin, N.J. Kennedy, R.J. Davis, and J.D. Richter. 2006. Control of cellular senescence by CPEB. Genes & Development 20 (19): 2701–2712.  https://doi.org/10.1101/gad.1438906.CrossRefGoogle Scholar
  8. 8.
    Groisman, I., M.Y. Jung, M. Sarkissian, Q. Cao, and J.D. Richter. 2002. Translational control of the embryonic cell cycle. Cell 109 (4): 473–483.CrossRefGoogle Scholar
  9. 9.
    Groppo, R., and J.D. Richter. 2011. CPEB control of NF-kappaB nuclear localization and interleukin-6 production mediates cellular senescence. Molecular and Cellular Biology 31 (13): 2707–2714.  https://doi.org/10.1128/MCB.05133-11.CrossRefGoogle Scholar
  10. 10.
    Holzer, N., D. Salvo, A.C. Marijnissen, K.L. Vincken, A.C. Ahmad, E. Serra, P. Hoffmeyer, R. Stern, A. Lubbeke, and M. Assal. 2015. Radiographic evaluation of posttraumatic osteoarthritis of the ankle: the Kellgren-Lawrence scale is reliable and correlates with clinical symptoms. Osteoarthritis and Cartilage 23 (3): 363–369.  https://doi.org/10.1016/j.joca.2014.11.010.CrossRefGoogle Scholar
  11. 11.
    Horisberger, M., B. Hintermann, and V. Valderrabano. 2009. Alterations of plantar pressure distribution in posttraumatic end-stage ankle osteoarthritis. Clinical Biomechanics (Bristol, Avon) 24 (3): 303–307.  https://doi.org/10.1016/j.clinbiomech.2008.12.005.CrossRefGoogle Scholar
  12. 12.
    Horisberger, M., V. Valderrabano, and B. Hintermann. 2009. Posttraumatic ankle osteoarthritis after ankle-related fractures. Journal of Orthopaedic Trauma 23 (1): 60–67.  https://doi.org/10.1097/BOT.0b013e31818915d9.CrossRefGoogle Scholar
  13. 13.
    Ivshina, M., I.M. Alexandrov, A. Vertii, S. Doxsey, and J.D. Richter. 2015. CPEB regulation of TAK1 synthesis mediates cytokine production and the inflammatory immune response. Molecular and Cellular Biology 35 (3): 610–618.  https://doi.org/10.1128/MCB.00800-14.CrossRefGoogle Scholar
  14. 14.
    Ivshina, M., P. Lasko, and J.D. Richter. 2014. Cytoplasmic polyadenylation element binding proteins in development, health, and disease. Annual Review of Cell and Developmental Biology 30: 393–415.  https://doi.org/10.1146/annurev-cellbio-101011-155831.CrossRefGoogle Scholar
  15. 15.
    Johnson, V.L., and D.J. Hunter. 2014. The epidemiology of osteoarthritis. Best Practice & Research. Clinical Rheumatology 28 (1): 5–15.  https://doi.org/10.1016/j.berh.2014.01.004.CrossRefGoogle Scholar
  16. 16.
    Kapoor, M., J. Martel-Pelletier, D. Lajeunesse, J.P. Pelletier, and H. Fahmi. 2011. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nature Reviews Rheumatology 7 (1): 33–42.  https://doi.org/10.1038/nrrheum.2010.196.CrossRefGoogle Scholar
  17. 17.
    Kellgren, J.H., and J.S. Lawrence. 1958. Osteo-arthrosis and disk degeneration in an urban population. Annals of the Rheumatic Diseases 17 (4): 388–397.CrossRefGoogle Scholar
  18. 18.
    Kim, J.H., J. Jeon, M. Shin, Y. Won, M. Lee, J.S. Kwak, G. Lee, J. Rhee, J.H. Ryu, C.H. Chun, and J.S. Chun. 2014. Regulation of the catabolic cascade in osteoarthritis by the zinc-ZIP8-MTF1 axis. Cell 156 (4): 730–743.  https://doi.org/10.1016/j.cell.2014.01.007. CrossRefGoogle Scholar
  19. 19.
    Kwon, Dohee, Sehui Kim, Pil-Jong Kim, Heounjeong Go, Soo Jeong Nam, Jin Ho Paik, Young A. Kim, Tae Min Kim, Dae Seog Heo, and Chul Woo Kim. 2016. Clinicopathological analysis of programmed cell death 1 and programmed cell death ligand 1 expression in the tumour microenvironments of diffuse large B cell lymphomas. Histopathology 68 (7): 1079–1089.CrossRefGoogle Scholar
  20. 20.
    Largo, R., M.A. Alvarez-Soria, I. Diez-Ortego, E. Calvo, O. Sanchez-Pernaute, J. Egido, and G. Herrero-Beaumont. 2003. Glucosamine inhibits IL-1beta-induced NFkappaB activation in human osteoarthritic chondrocytes. Osteoarthritis and Cartilage 11 (4): 290–298.CrossRefGoogle Scholar
  21. 21.
    Lin, C.L., V. Evans, S. Shen, Y. Xing, and J.D. Richter. 2010. The nuclear experience of CPEB: Implications for RNA processing and translational control. RNA 16 (2): 338–348.  https://doi.org/10.1261/rna.1779810.CrossRefGoogle Scholar
  22. 22.
    Malemud, C.J. 2006. Matrix metalloproteinases (MMPs) in health and disease: an overview. Frontiers in Bioscience 11: 1696–1701.CrossRefGoogle Scholar
  23. 23.
    Murphy, M.K., D.J. Huey, J.C. Hu, and K.A. Athanasiou. 2015. TGF-beta1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells. Stem Cells 33 (3): 762–773.  https://doi.org/10.1002/stem.1890.CrossRefGoogle Scholar
  24. 24.
    Nagaoka, K., K. Fujii, H. Zhang, K. Usuda, G. Watanabe, M. Ivshina, and J.D. Richter. 2016. CPEB1 mediates epithelial-to-mesenchyme transition and breast cancer metastasis. Oncogene 35 (22): 2893–2901.  https://doi.org/10.1038/onc.2015.350.CrossRefGoogle Scholar
  25. 25.
    Novoa, I., J. Gallego, P.G. Ferreira, and R. Mendez. 2010. Mitotic cell-cycle progression is regulated by CPEB1 and CPEB4-dependent translational control. Nature Cell Biology 12 (5): 447–456.  https://doi.org/10.1038/ncb2046.CrossRefGoogle Scholar
  26. 26.
    Park, S.Y., Y.C. Yoon, J.G. Cha, and K.S. Sung. 2016. T2 relaxation values of the Talar trochlear articular cartilage: Comparison between patients with lateral instability of the ankle joint and healthy volunteers. AJR. American Journal of Roentgenology 206 (1): 136–143.  https://doi.org/10.2214/AJR.15.14364.CrossRefGoogle Scholar
  27. 27.
    Saltzman, C.L., M.L. Salamon, G.M. Blanchard, T. Huff, A. Hayes, J.A. Buckwalter, and A. Amendola. 2005. Epidemiology of ankle arthritis: report of a consecutive series of 639 patients from a tertiary orthopaedic center. The Iowa Orthopaedic Journal 25: 44–46.Google Scholar
  28. 28.
    Sandell, L.J., and T. Aigner. 2001. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Research 3 (2): 107–113.  https://doi.org/10.1186/ar148. CrossRefGoogle Scholar
  29. 29.
    Smith, M.D., S. Triantafillou, A. Parker, P.P. Youssef, and M. Coleman. 1997. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. The Journal of Rheumatology 24 (2): 365–371.Google Scholar
  30. 30.
    Tay, J., and J.D. Richter. 2001. Germ cell differentiation and synaptonemal complex formation are disrupted in CPEB knockout mice. Developmental Cell 1 (2): 201–213.CrossRefGoogle Scholar
  31. 31.
    Thomas, A.C., T. Hubbard-Turner, E.A. Wikstrom, and R.M. Palmieri-Smith. 2017. Epidemiology of posttraumatic osteoarthritis. Journal of Athletic Training 52 (6): 491–496.  https://doi.org/10.4085/1062-6050-51.5.08.CrossRefGoogle Scholar
  32. 32.
    Udagawa, T., N.G. Farny, M. Jakovcevski, H. Kaphzan, J.M. Alarcon, S. Anilkumar, M. Ivshina, J.A. Hurt, K. Nagaoka, V.C. Nalavadi, L.J. Lorenz, G.J. Bassell, S. Akbarian, S. Chattarji, E. Klann, and J.D. Richter. 2013. Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology. Nature Medicine 19 (11): 1473–1477.  https://doi.org/10.1038/nm.3353. CrossRefGoogle Scholar
  33. 33.
    Valderrabano, V., M. Horisberger, I. Russell, H. Dougall, and B. Hintermann. 2009. Etiology of ankle osteoarthritis. Clinical Orthopaedics and Related Research 467 (7): 1800–1806.  https://doi.org/10.1007/s11999-008-0543-6.CrossRefGoogle Scholar
  34. 34.
    van der Sluijs, J.A., R.G. Geesink, A.J. van der Linden, S.K. Bulstra, R. Kuyer, and J. Drukker. 1992. The reliability of the Mankin score for osteoarthritis. Journal of Orthopaedic Research 10 (1): 58–61.  https://doi.org/10.1002/jor.1100100107.CrossRefGoogle Scholar
  35. 35.
    Yang, S., J. Kim, J.H. Ryu, H. Oh, C.H. Chun, B.J. Kim, B.H. Min, and J.S. Chun. 2010. Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nature Medicine 16 (6): 687–693.  https://doi.org/10.1038/nm.2153.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Lei Li
    • 1
    Email author
  • Jiaping Lan
    • 1
  • Yongjie Ye
    • 1
  • Bo Yang
    • 1
  • Xiaoyong Yang
    • 2
  • Zhijun Cai
    • 2
  1. 1.Department of OrthopaedicsSuining Central HospitalSuiningChina
  2. 2.Kunming General Hospital of Chinese PLATrauma Orthopedic Institute of Chinese PLAKunmingChina

Personalised recommendations