BACKGROUND: Glucocorticoid-induced osteoporosis is characterized by decreased osteoblastic activity and replacement of bone marrow with adipocytes. Since osteoblast and adipocytes are derived from the same mesenchymal stem cell, one might speculate that there is an interaction between these two cells types. In fact, leptin that is secreted from adipocytes is known to stimulate differentiation of osteoblasts, while it inhibits the differentiation of adipocytes. Furthermore, it has been demonstrated that PPAR is present in osteoblasts and it is increased by leptin in adipocytes. However, the role of PPAR and leptin remains unknown in glucocorticoid-induced osteoporosis. The aims of this study are to investigate the effect of glucocorticoid on bone mineral density and gene expression in osteoblasts and adipocytes, and to study the role of PPAR and leptin in the mechanism of glucocorticoid-induced osteoporosis. METHODS: Methylprednisolone, 1 mg/200 g-weight, was injected into five rats (steroid group) and saline was given to five rats (control group) for eight weeks. The bone mineral density was determined by dual energy X-ray absoptiometry. Gene expression of osteocalcin, alkaline phosphatase, lipoptrotein lipase, and PPAR -2 was assessed by RT-PCR. Serum leptin level was measured using a commercial radioimmunoassay kit. RESULTS: 1) The body weight of the steroid group was significantly lower than that of the control group (451.4+/-12.9 g vs. 247.6+/-19.8 g, p<0.05). The bone mineral density of the steroid group tended to be lower than that of the control group (0.27+/-0.01 g/cm2 vs. 0.26+/-0.01 g/cm2, p>0.05). 2) In the steroid group, the gene expressions of osteocalcin (1.00+/-0.08 vs. 0.23+/-0.16, p<0.05) and alkaline phosphatase (0.47+/-0.07 vs. 0.33+/-0.18, p<0.05) were decreased significantly compared to those in controls. 3) In the steroid group, the gene expression of lipoprotein lipase (0.23+/-0.06 vs. 0.39+/-0.12, p>0.05) and+/-PAR 2 (0.17+/-0.08 vs. 0.22+/-0.12, p>0.05) tended to be increased compared to that in the contol group. 4) The serum leptin level of the steroid group tended to be lower than that of the control group (0.20+/-0.12 g/L vs. 0.10+/-0.09 g/L, p>0.05). CONCLUSION: These data suggest that long-term administration of a large dose of glucocorticoid suppresses differentiation of osteoblasts and enhances the differentiation of adipocytes, which may be mediated by increased expression of PPAR and decreased synthesis of leptin.
Adipocytes ; Alkaline Phosphatase ; Animals ; Body Weight ; Bone Density ; Bone Marrow* ; Gene Expression ; Leptin ; Lipase ; Lipoprotein Lipase ; Mesenchymal Stromal Cells* ; Methylprednisolone ; Osteoblasts ; Osteocalcin ; Osteoporosis ; Peroxisome Proliferator-Activated Receptors ; Radioimmunoassay ; Rats