Role of cAMP in phenotypic changes of osteoblasts

Bone remodeling is precisely controlled by bone formation and bone resorption, and osteoblasts are responsible for both processes. Osteoblasts exhibit an osteoclastogenic phenotype in response to elevated intracellular cyclic AMP [cAMP]_i levels. However, the role of cAMP in osteoblasts acquiring an osteogenic phenotype is controversial. To elucidate the effect of cAMP on both phenotypes, an osteoblast-like cell line, TMS-12, was established in our laboratory and used in this study. Dibutyryl-cAMP (dBcAMP), a cAMP analogue, inhibited mineralization in TMS-12 cells and MC3T3E1 cells (an osteoblast-like cell line) but promoted osteoclast-supporting activity in TMS-12 cells. Moreover, mineralization was inhibited in glucagon receptor-transduced TMS-12 cells (TMS-12GCGR) after glucagon treatment to increase endogenous [cAMP]_i levels. However, the osteoclast-supporting activity of TMS-12GCGR cells was stimulated by glucagon treatment. These cAMP-induced phenotypic changes of osteoblasts were also supported by their gene expression profile. These results suggest that [cAMP]_i is an important factor mediating phenotypic changes of osteoblasts. Our findings may provide valuable insights into the mechanisms that underlie bone remodeling in both, healthy and diseased states.