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Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation
Xiao-Feng Liu1, Yi-Tao Liao1, Jia-Hao Shao1
1Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Background:
Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear.
Methods:
We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection.
Results:
Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts.
Conclusions:
Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.
Insights
Angelicin, a compound from Psoralea, prevents osteoporosis by inhibiting osteoclast formation. It works by increasing KAT6A expression, activating the Nrf2/HO-1 antioxidant system, and reducing oxidative stress in osteoclasts.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Osteoporosis is characterized by excessive osteoclast formation.
- The precise mechanism by which angelicin prevents osteoporosis is not fully understood.
- Angelicin, derived from Psoralea, shows potential in mitigating osteoporosis.
Purpose of the Study:
- To investigate the effect of angelicin on osteoclast oxidative stress.
- To elucidate the mechanism of angelicin's action in preventing osteoclast formation.
- To evaluate angelicin's impact on bone mass and osteoclast activity in vivo and in vitro.
Main Methods:
- Ovariectomized osteoporosis model rats and RAW264.7 cells were used to assess angelicin's effects.
- Bone mineral density was analyzed using H&E staining and micro-CT.
- Reactive oxygen species (ROS) levels, osteoclast-related gene/protein expression, and osteoclast differentiation were examined.
Main Results:
- Angelicin treatment increased bone mineral density and reduced osteoclast numbers in rats.
- In vitro, angelicin inhibited osteoclast differentiation and decreased ROS levels.
- Angelicin upregulated KAT6A, HO-1, and Nrf2, while downregulating osteoclast-specific genes like MMP9 and NFATc1.
Conclusions:
- Angelicin enhances KAT6A expression, which activates the Nrf2/HO-1 antioxidant pathway.
- This activation leads to reduced ROS levels and inhibition of osteoclast formation.
- Angelicin effectively mitigates oxidative stress and prevents osteoclastogenesis, offering a potential therapeutic strategy for osteoporosis.
