Parathyroid Hormone Induction of Cyclooxygenase-2 Expression in Human Osteoblasts Depends on Both Cyclic AMP and Calcium-Dependent Pathways

Parathyroid hormone (PTH) increases serum Ca2+ concentration, and one of the mechanisms leading to this result is the induction of osteoclast activity and consequent bone resorption. Although the presence of PTH in osteoclasts is polemic, functional studies have shown that induction of bone resorption by this hormone depends on the presence of osteoblasts1, on soluble factors released by these cells2, and probably on direct contact between osteoblasts and osteoclasts3. Prostaglandins are probably implicated in the cross-talk between osteoblasts and osteoclasts: their production by osteoblasts is induced by mechanical stress4, IL-1 and TNF5, and PTH6, and PGE2 can stimulate both bone formation and resorption7. The mechanism implicated in the control of prostaglandin production by PTH, however, has not been elucidated. Since availability of cyclooxygenases is a rate-limiting step in the synthesis of prostaglandins, our objective was to verify if cyclooxygenase-2 (COX-2) expression in human osteoblasts in culture could be regulated by PTH, and to study the intracellular mechanisms implicated in this action.