Title

The role of cyclooxygenase-2 in osteoblast proliferation and apoptosis

Date of Completion

January 2007

Keywords

Biology, Cell|Health Sciences, Oncology

Degree

Ph.D.

Abstract

COX-2 is highly expressed in osteoblasts and prostaglandins (PGs) produced by COX-2 can be potent stimulators of both bone resorption and bone formation. Overexpression of COX-2 is generally considered to promote tumorigenesis. The goals of this work were to determine the role of endogenous COX-2 expression in osteoblastic proliferation and apoptosis and to evaluate the potential role of COX-2 in osteosarcoma. First, we analyzed proliferation and apoptosis in primary calvarial osteoblast cultures from COX-2 wild type (COX-2 +/+, WT) and COX-2 knockout (COX-2 -/-, KO) mice. Increased cell number and DNA synthesis, associated with decreased G0/G1 and increased S cell cycle distribution, were detected in COX-2 KO cultures compared with COX-2 WT cultures. There was no effect of COX-2 expression, inhibition of PG production, or addition of PGE2 on apoptosis. Retroviral expression of COX-2 in KO cells also decreased cell growth and proliferation compared with control cells, and these effects were reversed by inhibiting COX activity. These results suggest that endogenous COX-2 gene expression and PG production in primary calvarial osteoblast cultures decreases cell proliferation with no effect on apoptosis. ^