Background and Purpose: Osteoclasts play a pivotal role in diseases such as osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast‐related diseases. Here, we examined changes in osteoclastogenesis and LPS‐induced osteolysis in response to andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata.Experimental Approach: Effects of AP on osteoclast differentiation and bone resorption were measured in vitro. Western blots and RT‐PCR techniques were used to examine the underlying molecular mechanisms. The bone protective activity of AP in vivo was assessed in a mouse model of osteolysis.Key Results: AP concentration‐dependently suppressed RANKL‐mediated osteoclast differentiation and bone resorption in vitro and reduced the expression of osteoclast‐specific markers, including tartrate‐resistant acid phosphatase, calcitonin receptors and cathepsin K. Further molecular analysis revealed that AP impaired RANKL‐induced NF‐κB signalling by inhibiting the phosphorylation of TGF‐β‐activated kinase 1, suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the nuclear translocation of the NF‐κB p65 subunit. AP also inhibited the ERK/MAPK signalling pathway without affecting p38 or JNK signalling.Conclusions and Implications: AP suppressed RANKL‐induced osteoclastogenesis through attenuating NF‐κB and ERK/MAPK signalling pathways in vitro, thus preventing bone loss in vivo. These data indicated that AP is a promising natural compound for the treatment of osteoclast‐related bone diseases.
Hydrogels with organized structure have attracted remarkable attentions for bio-related applications. Among the preparation of hierarchical hydrogel materials, fabrication of hydrogel with multi-layers is an important branch. Although the generation mechanism of layers had been fully discussed, sub-layer structure was not sufficiently studied. In this research, multi-layered chitosan hydrogel with oriented structure was constructed and the formation mechanism of orientation was proposed, based on gelation behavior and entanglement of polymer chains in the hydrogel-solution system. Employing the layered-oriented characteristic, chitosan hydrogel materials with various shapes and structure can be designed and fabricated.
Discography often destroys the hypoxic environment in the intervertebral disc and accelerates intervertebral disc degeneration (IVDD). Therefore, it often fails to meet the requirements for application in clinical practice. This technology mainly increases the reactive oxygen species (ROS) in the IVD. As so, it is particularly critical to develop strategies to avoid this degeneration mechanism. Prussian blue nanoparticles (PBNPs) are found to enhance development under magnetic resonance T1 and have antioxidant enzyme activity. The key results of the present study confirm that PBNPs alleviate intracellular oxidative stress and increase the intracellular activities of antioxidant enzymes, such as superoxide dismutase 1 (SOD1). PBNPs can rescue nucleus pulposus cell degeneration by increasing oxidoreductase system‐related mRNA and proteins, especially by stabilizing SOD1 from ubiquitination‐proteasome degradation, thus improving the mitochondrial structure to increase antioxidation ability, and finally rescuing ROS‐induced IVDD in a rat model. Therefore, it is considered that PBNPs can be a potential antioxidation‐protective discography contrast agent.