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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Greenberg ME, Ziff EB (1984) Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature (Lond) 311:433–438
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
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
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
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
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
Wroblewski J, Edwall-Arvidsson C (1995) Inhibitory effects of basic fibroblast growth factor on chondrocyte differentiation. J Bone Miner Res 10:735–742
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
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
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
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
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
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
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
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
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights 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