Boldine Ameliorates Estrogen Deficiency-Induced Bone Loss via Inhibiting Bone Resorption.

Osteoporosis is an enormous health problem caused by the imbalance between bone resorption and bone formation. The current therapeutic strategies for osteoporosis still have some limitations. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects in vivo. For the first time, we discover that boldine has a protective effect for the estrogen deficiency-induced bone loss in mice. According to the Micro-CT and histomorphometry assays, boldine conducts this protective effect through inhibiting bone resorption without affecting bone formation in vivo. Moreover, we showed that boldine can inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation via impairing the AKT signaling pathways, while SC79 (an AKT agonist) partially rescue this effect. In conclusion, our results suggest that boldine can prevent estrogen deficiency-induced osteoporosis by inhibiting osteoclastogenesis. Thus, boldine may be served as a novel therapeutic agent for anti-osteoporotic therapy.

Sophocarpine attenuates wear particle-induced implant loosening by inhibiting osteoclastogenesis and bone resorption via suppression of the NF-κB signalling pathway in a rat model.

BACKGROUND AND PURPOSE: Aseptic prosthesis loosening, caused by wear particles, is one of the most common causes of arthroplasty failure. Extensive and over-activated osteoclast formation and physiological functioning are regarded as the mechanism of prosthesis loosening. Therapeutic modalities based on inhibiting osteoclast formation and bone resorption have been confirmed to be an effective way of preventing aseptic prosthesis loosening. In this study, we have investigated the effects of sophocarpine (SPC, derived from Sophora flavescens) on preventing implant loosening and further explored the underlying mechanisms. EXPERIMENTAL APPROACH: The effects of SPC in inhibiting osteoclastogenesis and bone resorption were evaluated in osteoclast formation, induced in vitro by the receptor activator of NF-κB ligand (RANKL). A rat femoral particle-induced peri-implant osteolysis model was established. Subsequently, micro-CT, histology, mechanical testing and bone turnover were used to assess the effects of SPC in preventing implant loosening. KEY RESULTS: In vitro, we found that SPC suppressed osteoclast formation, bone resorption, F-actin ring formation and osteoclast-associated gene expression by inhibiting NF-κB signalling, specifically by targeting IκB kinases. Our in vivo study showed that SPC prevented particle-induced prosthesis loosening by inhibiting osteoclast formation, resulting in reduced periprosthetic bone loss, diminished pseudomembrane formation, improved bone-implant contact, reduced bone resorption-related turnover and enhanced stability of implants. Inhibition of NF-κB signalling by SPC was confirmed in vivo. CONCLUSION AND IMPLICATIONS: SPC can prevent implant loosening through inhibiting osteoclast formation and bone resorption. Thus, SPC might be a novel therapeutic agent to prevent prosthesis loosening and for osteolytic diseases.