Oroxin B Attenuates Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Formation and Activity.

BACKGROUND: Osteoclasts are the major players in bone resorption and have always been studied in the prevention and treatment of osteoporosis. Previous studies have confirmed that a variety of flavonoids inhibit osteoporosis and improve bone health mainly through inhibiting osteoclastogenesis. Oroxin B (OB) is a flavonoid compound extracted from traditional Chinese herbal medicine Oroxylum indicum (L.) Vent, exerts potent antitumor and anti-inflammation effect, but its effect on osteoclastogensis remains unknown. METHODS: We comprehensively evaluated the effect of OB on the formation and function of osteoclasts and the underling mechanism by bone marrow-derived macrophage in vitro. In vivo, we used mice ovariectomized model to verify the protective effect of OB. RESULTS: OB was found to inhibit osteoclast formation and bone resorption function in vitro, in a dose-dependent manner and the increased osteoclastic-related genes induced by RANKL (NFATc1, c-fos, cathepsin K, RANK, MMP9 and TRAP) were also attenuated following OB treatment. Mechanistical investigation showed OB abrogated the increased phosphorylation level of MAPK and NF-κB pathway, and diminished the expression of the vital transcription factors for osteoclastogenesis. OB also prevented ovariectomy (OVX)-induced bone loss by inhibiting osteoclast formation and activity in mice. CONCLUSION: Our study demonstrated that OB may act as an anti-osteoporosis agent by inhibiting osteoclast maturation and attenuating bone resorption.

Protective effects of total saponins of panax notoginseng on steroid-induced avascular necrosis of the femoral head in vivo and in vitro.

This research was designed to investigate the protective effects of TSPN on steroid-induced avascular necrosis of the femoral head (ANFH) and the likely mechanisms of those effects. As an in vivo study, TSPN was shown to be protective against steroid-induced ANFH due to the upregulation of VEGF-A. Furthermore, TSPN attenuated the apoptosis of osteocytes and reduced the expression of Caspase-3 relative to the model group. As an in vitro study, TSPN exerted a concentration-dependent protective effect against apoptosis in MC3T3-E1 cells. Moreover, TSPN (at a dose of 100 µg/mL) significantly reversed the dexamethasone-induced augmentation of Caspase-3 expression and activity. Therefore, our study demonstrated that TSPN had a protective effect against steroid-induced ANFH that was related to the upregulation of VEGF-A and the inhibition of apoptosis and Caspase-3 activation.

Effect of rifampicin on the risk of steroid-induced osteonecrosis of the femoral head.

OBJECTIVE: To investigate the effects and possible mechanism of rifampicin on steroid-induced osteonecrosis of the femoral head (ONFH). METHODS: Bone marrow stromal cells (BMSC) separated from male rats were cultured in vitro without any treatment (Group mA), exposed to dexamethasone (Group mB), treated with rifampicin (Group mC), and exposed to dexamethasone and rifampicin simultaneously (Group mD) respectively (n = 5 in each group). After 7 days, P-glycoprotein (P-gp) activity and adipogenesis of the BMSC were evaluated. In an in vivo experiment, 80 rats were randomly divided into 4 groups (n= 20 in each group). Group A received intragastric saline for 5 weeks. Group B received intragastric saline for one week, followed by subcutaneous methylprednisolone and saline for 4 weeks. Group C received intragastric rifampicin for 5 weeks. Group D received intragastric rifampicin for one week, followed by subcutaneous methylprednisolone and rifampicin for 4 weeks. At the end of the experiment, all rats underwent analysis of P-gp activity of BMSC, P-gp expression in the femoral heads, MRI and histomorphometry of the femoral heads. RESULTS: In vitro, the P-gp activity of BMSC increased and lipid accumulation decreased significantly in Group mD, compared to Group mB. In vivo, P-gp activity and P-gp expression in Group D increased compared to Group B. The mean area of MRI abnormal signal, adipocytic variables and apoptotic cells in Group D decreased, mean percentage of the whole epiphysis made up by the epiphyseal ossification center and trabecular structure variables improved compared to those in Group B. The incidence of ONFH was lower in Group D (50%) than in Group B (80%). CONCLUSION: Rifampicin may decrease the risk of steroid-induced ONFH by enhancing P-gp activity, thus preventing steroid-induced BMSC adipogenesis.