The biological roles of extracellular and intracytoplasmic glucocorticoids in skeletal cells.

Osteoporosis is the most common metabolic disease characterized by loss of the normal density of bone, resulting in fragile bone and a higher risk of fractures. Patients under glucocorticoids treatment are susceptible to glucocorticoid-induced osteoporosis (GIO). The normal bone turnover depends on a balance between osteoblasts and osteoclasts. The skeletal cells including osteoblasts, osteoclasts, osteocytes and their precursors demonstrate altered features while they are cocultured with different extracellular glucocorticoids, or their intracytoplasmic glucocorticoids modified by genetic manipulation of 11beta-HSD isozyme. However, recent studies have also demonstrated different or even contradictive outcomes on whether the glucocorticoids inhibit or increase biological activity of these skeletal cells. Focusing on the roles of extracellular glucorticoids, intracytoplasmic glucocorticoids and the mechanism of transmembrane passage of the glucocorticoids, this review reveals that glucocorticoids may exert either inhibitive or enhancing influence on these skeletal cells, but relying on the difference in cell origins, methodology, and types of glucocorticoids. In addition, the effects of glucocorticoids may be dose- and time-dependent.