gms | German Medical Science

Objectives: Osteonecrosis of femoral head (ONFH) is commonly associated with bone collapsion, bone resorption, and vascular interruption. It involves excessive resorption of bone matrix by activated osteoclasts. Bajijiasu, a natural compound derived from Morinda officinalis F.C. How, has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear. Identification of Bajijiasu for inhibiting osteoclast formation is essential for the treatment of ONFH.

Methods: In present study, we set up an ONFH rat model that used to investigate the therapeutic effects of Bajijiasu on osteonecrosis by using micro-computed tomography (micro-CT) and histopathological examination. Further, bone marrow-derived osteoclast culture was used to examine the inhibitory effect of Bajijiasu on osteoclasts inhibition. Real time PCR was employed to evaluate the effect of Bajijiasu on the expression of osteoclast marker genes. The activities of transcriptional factors NF-kB and NFATc1 were evaluated using a luciferase reporter assay, and the proteins level in RANKL signaling pathways was analyzed by Western blot.

Results and Conclusion: In the present study, we found that Bajijiasu dose-dependently inhibited RANKL induced osteoclast formation and bone resorption from 0.1mM, and reached half maximal inhibitory effects (IC50) at 0.4mM without toxicity. Expression of RANKL induced osteoclast specific marker genes including Ctsk, NFATc1, TRAcP, V-ATPase d2, and MMP2 was inhibited by Bajijiasu treatment. Luciferase reportor gene studies showed that Bajijiasu could significantly reduce the expression and transcriptional activity of NFAT as well as RANKL-induced NF-kB activation in a dose dependent manner. Further, Bajijiasu was found to decrease the RANKL induced phosphorylation of ERK, IkB-a, NFAT, and V-ATPase d2. In vivo study, we revealed that Bajijiasu abrogated steriod-induced osteonecrosis of femoral head. Taken together, this study revealed Bajijiasu could attenuate osteoclast formation and bone resorption by mediating RANKL signaling pathways, indicative of a potential effect of Bajijiasu on osteonecrosis of femoral head.