Osteoprotective Effect of Cimiracemate in Glucocorticoid-Induced Osteoporosis by Osteoprotegerin/Receptor Activator of Nuclear Factor κ B/Receptor Activator of Nuclear Factor Kappa-Β Ligand Signaling.

OBJECTIVES: Present investigation determines the protective effect of cimiracemate A against glucocorticoid-induced osteoporosis rat.

METHODS: Osteoporosis was induced by injecting methylprednisolone acetate (21 mg/kg) for the period of 6 weeks, and the rats were treated with cimiracemate A 5 and 10 mg/kg, p.o. 60 min after the administration of methylprednisolone acetate (21 mg/kg) for the duration of 6 weeks. Effect of cimiracemate A was observed by estimating the microarchitecture of bone and histopathological changes by micro-CT scan and light microscope. Moreover, lipid profile, mediators of inflammation, and parameters that affect bone formation were determined in the serum and western blot assay, and reverse transcription polymerase chain reaction was done for the estimation of protein expression in the bone tissues. Moreover, cytotoxic effect of cimiracemate A on bone marrow macrophages and bone marrow stromal cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.

RESULTS: Result of the investigation suggests that treatment with cimiracemate A ameliorates the microarchitecture of bone and histopathological changes in the glucocorticoid-induced osteoporosis rat. Level of lipid and mediators of inflammation was significantly reduced in the serum of cimiracemate A-treated rats than the negative control group. However, the activity of tartrate-resistant acid phosphatase and the level of collagen type I fragments in the serum were found to be reduced, and osteocalcin level was enhanced in cimiracemate A-treated rats than the negative control group. Moreover, treatment with cimiracemate A attenuates the expression of receptor activator of nuclear factor kappa-Β ligand (RANKL), receptor activator of nuclear factor κ B (RANK), and osteoprotegerin (OPG) protein in glucocorticoid-induced osteoporosis rats.

CONCLUSION: In conclusion, our study suggests that cimiracemate A protects the glucocorticoid-induced osteoporosis by regulating the RANKL/RANK/OPG signaling pathway.