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FUNCTIONAL ROLES OF THE WNT SIGNALING PATHWAY IN INTERVERTEBRAL DISC CELLS▪FBASED ON ANALYSIS OF THE PKC PATHWAY: GP15.

Arai, Fumiyuki; Hiyama, Akihiko; Sakai, Daisuke; Mochida, Joji

Spine Journal Meeting Abstracts: October 2011 - Volume - Issue - [no page #]
GENERAL POSTERS
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Orthopedics, Tokai University School of Medicine, Kanagawa, Japan

INTRODUCTION: Wnt signaling is thought to play a significant role in early developmental process and morphogenesis. We have been studying the Wnt/Àcatenin pathway and reported that it inhibits proliferation of intervertebral disc (IVD) cells. Although the non‐canonical pathway, PKC signaling, has not been fully elucidated, the cross‐talk between the two pathways may be crucial for the onset of IVD degeneration. Here we report on the functional roles of the PKC signaling pathway (non‐canonical pathway) in IVD cells.

METHODS: A total of 32 Sprague Dawley (SD) rats (12 weeks old) were used for this study. We measured the activity of Tcf reporter plasmid (Topflash) in nucleus pulposus (NP) cells after a PKC‐activator phorbolmyristate acetate (PMA) treatment. In addition, the effect of PKC signaling pathway on À‐catenin gene and protein expression was determined. After analyzing the proliferative potential of the IVD cells as well as the transcriptional activity and gene and protein expression of aggrecan, we evaluated glycosaminoglycan (GAG) synthesis due to activation of PKC signaling pathway.

RESULTS: PMA treatment inhibited the transcriptional activity of Topflash in the NP cells. Similar results were obtained from the gene and protein expression analysis. When NP cells were treated with PMA, a significant increase in viability was observed. Moreover, expression of aggrecan transcript, gene and protein were increased to PMA treatment. We also found that GAG synthesis in NP cells with PMA treatment was upregulated in a dose and time‐dependent manner.

DISCUSSION AND CONCLUSION: Activation of the PKC signaling pathway inhibited the Wnt/À‐catenin pathway and enhanced the proliferation of NP cells. Moreover, expression of aggrecan transcript, gene and proten was upregulated due to the activation of PKC signaling pathway. These results suggest that activation of the PKC signaling pathway can be the target for a new therapeutic approach against IVD degeneration.

© 2011 Lippincott Williams & Wilkins, Inc.