Electronic Thesis and Dissertation Repository

Degree

Master of Clinical Science

Program

Orthodontics

Supervisor

Dr. Jeffrey Dixon

Abstract

P2X7 is a cell-surface nucleotide receptor that plays a critical role in skeletal mechanotransduction; however, the signaling pathways mediating these effects are poorly understood. Previous studies showed that the nucleotide analog benzoylbenzoyl-ATP induces anabolic gene expression in osteoblastic cells. Our first objective was to determine whether this effect was mediated by P2X7. Inhibition of anabolic gene expression by a P2X7-specific antagonist established involvement of this receptor. Our second objective was to investigate the role of lipid mediators, lysophosphatidic acid (LPA) and prostaglandin (PG), both of which are produced in response to P2X7 activation. The effect of P2X7 on expression of the anabolic gene Ptgs2 was abolished by an LPA receptor antagonist or inhibition of PG synthesis. Furthermore, in the absence of nucleotide, LPA and PGE2 synergistically stimulated Ptgs2 expression. Thus, LPA and PG signaling pathways appear to be necessary and sufficient to mediate the effect of P2X7 on Ptgs2 expression.

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