Physiological Role of PGE2 and DBcAMP in Bone Cell Metabolism

Chae, Han Jung; Chae, Soo Wan; Kim, Hyung Ryong

Abstract

One of the primary functions for which bones have evolved is to act as a structural support. To achieve this, bones remodel throughout life so that their structure remains optimal for the prevailing mechanical environment. Bone remodeling consists of an initial phase of osteoclastic bone resorption followed by a bone formation period. Prostaglandins are potent regulators of bone formation and bone resorption that can have both stimulatory and inhibitory effects. Elevation of intracellular cAMP is an important intracellular signaling mechanism involved in the regulation of the expression of many proteins. In this study we examine whether PGE or DBcAMP affects osteoblastic activation or osteoclastic differentiation in mouse bone marrow cells and osteosarcoma ROS 17/2.8 cells. The effect of PGE and DBcAMP on the cell proliferation was measured by the incorporation of [3H]- thymidine into DNA. As a result, PGE2 (0.5-1 ug/ml) and DBcAMP (0.1-0.5 mM) inhibited the [3H]-thymidine incorporation into DNA in a dose dependent manner. The effect of PGE2 and DBcAMP on the induction of alkaline phosphatase (ALP) was investigated in ROS 17/2.8 cells cultured in medium containing 0.4% fetal bovine serum. PGE and DBcAMP stimulated ALP activity in the cells in a dose- dependent manner. PGE2 also increased the intracellular cAMP content in a dose- dependent fashion with a maximal effect at 0.5 ug/ml. ROS 17/2.8 cells release nitric oxide upon stimulation of PGE2 or DBcAMP with interferon-r. PGE2 and DBcAMP increase the phosphorylation level of CREB (cAMP response element binding protein) without any change on the amount of CREB protein. Also, PGE (10-6 M) and DBcAMP (10-4 M) significantly increase the generation of osteoclasts in mouse bone marrow cell culture system. In conclusion, the results of this study suggested that cAMP appears to be an important regulatory molecule in the processes of bone formation and resorption.