Skip to main content

Protein Kinase C-Activator Inhibits Progression of Osteoarthritis by Inhibiting c-Fos Protein Expression in Articular Chondrocytes

  • Conference paper
Advances in Osteoarthritis
  • 124 Accesses

Summary

Expression of the e-Fos protein was examined by immunohis-tochemistry in rat knee joints with surgically induced osteoarthritis. Cells stained for the c-Fos protein were not observed in the control knees. However, in early osteoarthritic joints, chondrocytes that expressed c-Fos protein were observed in all the articular cartilage layers on day 3 and in the residual superficial layers 2 weeks after surgery. Safranin-O staining of the matrix decreased in the superficial layers in which c-Fos-positive chondrocytes were identified. In those knee joints in which potent protein kinase C (PKC) agonist 12-o-tetradecanoylphorbol-13-acetate (TPA) was injected intraarticularly, significantly fewer histological osteoarthritic changes developed 2 and 4 weeks after surgery, and the numbers of chondrocytes that expressed c-Fos protein generally decreased and were observed mainly in the superficial layers even on day 3 and were not observed in any of the articular cartilage layers 2 and 4 weeks after surgery. Safranin-O staining was normally observed even 2 weeks after surgery. These chondroprotective effects of exogenous TPA appeared to be related to the inhibition of c-Fos protein synthesis in chondrocytes.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Greenberg ME, Ziff EB (1984) Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature (Lond) 311:433–438

    Article  CAS  Google Scholar 

  2. Kruijer W, Cooper JA, Hunter T, Verma IM (1984) Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature (Lond) 312:711–716

    Article  CAS  Google Scholar 

  3. Raab-Cullen DM, Thiede MA, Petersen DN, Kimmel DB, Recker RR (1994) Mechanical loading stimulates rapid changes in periosteal gene expression. Calcif Tissue Int 55:473–478

    Article  PubMed  CAS  Google Scholar 

  4. Boumediene K, Vivien D, Macro M, Bogdanowicz P, Lebrun E, Pujol J-P (1995) Modulation of rabbit articular chondrocyte (RAC) proliferation by TGF-β isoforms. Cell Prolif 28:221–224

    Article  PubMed  CAS  Google Scholar 

  5. Osaki M, Tsukazaki T, Okano K, Yamasita T, Iwasaki K (1995) c-fos gene regulation by TGF-β in rat articular chondrocytes. Nippon Seikeigeka Gakkai Zasshi (J Jpn Orthop Assoc) 69:S1738

    Google Scholar 

  6. Machwate M, Jullienne A, Moukhtar M, Lomri A, Marie P (1995) c-fos protooncogene is involved in the mitogenic effect of transforming growth factor-β in osteoblastic cells. Mol Endocrinol 9:187–198

    Google Scholar 

  7. Wroblewski J, Edwall-Arvidsson C (1995) Inhibitory effects of basic fibroblast growth factor on chondrocyte differentiation. J Bone Miner Res 10:735–742

    Article  PubMed  CAS  Google Scholar 

  8. Gilman MZ (1988) The c-fos serum response element responds to protein kinase C-dependent and -independent signals but not to cyclic AMP. Genes Dev 2:394–402

    Article  PubMed  CAS  Google Scholar 

  9. McDonnell SE, Kerr LD, Matrisian LM (1990) Epidermal growth factor stimulation of stromelysin mRNA in rat fibroblasts requires induction of proto-oncogenes c-fos and c-jun and activation of protein kinase C. Mol Cell Bio 10:4284–4293

    CAS  Google Scholar 

  10. Hamanishi C, Hashima M, Satsuma H, Tanaka S (1996) Protein kinase C-activator inhibits progression of osteoarthritis induced in rabbit knee joints. J Clin Lab Med 127:540–544

    Article  CAS  Google Scholar 

  11. Schmitz JP, Schwartz Z, Sylvia VL, Dean DD, Calderon F, Boyan BD (1996) Vitamin D3 regulation of stromelysin-1 (MMP-3) in chondrocyte cultures is mediated by protein kinase C. J Cell Physiol 168:570–579

    Article  PubMed  CAS  Google Scholar 

  12. Yoshimi T, Kikuchi T, Obara T, et al (1994) Effects of high-molecular-weight sodium hyaluronate on experimental osteoarthrosis induced by the resection of rabbit anterior cruciate ligament. Clin Orthop Relat Res 298:296–304

    PubMed  Google Scholar 

  13. Kerr LD, Magun BE, Matrisian LM (1992) The role of C-Fos in growth factor regulation of stromelysin/transin gene expression. Matrix l(suppl):176–183

    Google Scholar 

  14. Tsuji M, Funahashi S, Takigawa M, Seiki M, Fujii K, Yoshida T (1996) Expression of c-fos gene inhibits proteoglycan synthesis in transfected chondrocyte. FEBS Lett 381:222–226

    Article  PubMed  CAS  Google Scholar 

  15. Satsuma H, Saitou N, Hamanishi C, Hashima M, Tanaka S (1996) Alpha and epsilon isozymes of protein kinase C in the chondrocytes in normal and early osteoarthritic articular cartilage. Calcif Tissue Int 58:192–194

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Tokyo

About this paper

Cite this paper

Hamanishi, C., Miyazaki, H., Satsuma, H., Tanaka, S. (1999). Protein Kinase C-Activator Inhibits Progression of Osteoarthritis by Inhibiting c-Fos Protein Expression in Articular Chondrocytes. In: Tanaka, S., Hamanishi, C. (eds) Advances in Osteoarthritis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68497-8_14

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-68497-8_14

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68499-2

  • Online ISBN: 978-4-431-68497-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics