Rubiadin Regulates Bone Metabolism in Ovariectomized Rat Model by Inhibition of osteoclast formation and differentiation

Abstract

AbstractThe present study investigated the effect of rubiadin from morinda officinalis on bone metabolism in an ovariectomized rat model. Results from the MTT test showed that the best drug concentration was 0.6 mg for 24 h (P>0.05). Compared with the Control group, the femoral bone mineral density in the experimental group treated with rubiadin was significantly higher (P<0.05). After the intervention of rubiadin, the level of P1NP in serum increased, the level of β‐CTX decreased, and the level of estradiol increased. The up‐regulated genes C−C motif chemokine ligand 2 (CCL2), Inhibitor of Nuclear Factor Kappa B Kinase Subunit Beta (IKBKB), C1q, C6, Suppressor of cytokine signaling1 (SOCS1/3) and Dickkopf‐3 (DKK3) were screened from the data. Down regulated genes wnt6, Sfrp5, COL4A6, Ig like R. The differential genes were detected by RT‐PCR. Compared with the Control group, CCL2 and SOCS3 were significantly up‐regulated in the experimental group (P<0.05), and COL4A6 and LILRB3a were significantly down regulated in the experimental group (P<0.05). Western blot test results showed that the expression of LILRB3a protein was significantly reduced, while the expression of SOCS3 protein was significantly increased, indicating that rubiadin could significantly increase the expression of SOCS3 protein and reduce the expression of LILRB3a protein. In conclusion, rubiadin inhibits the formation and differentiation of osteoclasts by affecting the expression of CCL2 and SOCS3, COL4A6 and LILRB3a genes. Therefore, rubiadin can be of therapeutic importance for the treatment of osteoporosis.