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Osthole Inhibits M1 Macrophage Polarization and Attenuates Osteolysis in a Mouse Skull Model
Feifei Wang1, Peiming Yang2, Tianhao Wan3
1The Affiliated Tai'an City Central Hospital of Qingdao University, Tai'an, 271000 Shandong Province, China.
Abstract:
Excessive bone resorption due to increased inflammatory factors is a common feature of inflammatory lytic bone diseases. This group of diseases is effectively treated with drugs. In recent years, many studies have reported that traditional Chinese medicine herbs have substantial effects on inflammation, osteoclast differentiation and maturation, and bone destruction. Herein, we investigated the effects of osthole (OST) on lipopolysaccharide- (LPS-) induced macrophage polarization, inflammatory responses, and osteolysis. In vitro, we used immunofluorescence and quantitative real-time polymerase chain reaction assays to confirm whether bone marrow-derived macrophages showed an increased expression of inflammatory factors, such as interleukin-6, iNOS, CCR7, and CD86, in the presence of LPS. However, we found that such expression was suppressed and that the M2 macrophage expression increased in the presence of OST. OST reduced LPS- and RANKL-induced intracellular reactive oxygen species production in the bone marrow-derived macrophages. Further, it potently suppressed osteoclast differentiation and osteoclast-specific gene expression by suppressing the P38/MAPK and NF-κB pathways. Consistent with the in vitro observations, OST greatly ameliorated LPS-induced bone resorption and modulated the ratio of macrophages at the site of osteolysis. Taken together, OST has great potential for use in the management of osteolytic diseases.
Insights
Osthole (OST) suppresses inflammatory responses and osteoclast formation in inflammatory lytic bone diseases. This traditional Chinese medicine herb shows potential for managing bone destruction by modulating macrophage polarization and key signaling pathways.
Area of Science:
- * Pharmacology and Immunology
- * Molecular Biology
- * Traditional Chinese Medicine
Background:
- * Inflammatory lytic bone diseases are characterized by excessive bone resorption driven by inflammatory factors.
- * Traditional Chinese medicine herbs are increasingly recognized for their anti-inflammatory and bone-protective properties.
- * Osthole (OST) is a compound from traditional Chinese medicine with potential therapeutic applications.
Purpose of the Study:
- * To investigate the effects of osthole (OST) on lipopolysaccharide (LPS)-induced macrophage polarization and inflammatory responses.
- * To determine OST's impact on osteoclast differentiation and osteolysis.
- * To elucidate the underlying molecular mechanisms, including signaling pathways involved.
Main Methods:
- * In vitro studies using bone marrow-derived macrophages treated with LPS and OST.
- * Immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR) assays to assess inflammatory markers and macrophage polarization.
- * Measurement of intracellular reactive oxygen species (ROS) production.
- * Analysis of osteoclast differentiation and gene expression.
- * Investigation of the P38/MAPK and NF-κB signaling pathways.
- * In vivo assessment of OST's effect on LPS-induced bone resorption.
Main Results:
- * OST suppressed the LPS-induced expression of pro-inflammatory factors (interleukin-6, iNOS, CCR7, CD86) in macrophages.
- * OST promoted M2 macrophage polarization and reduced intracellular ROS production.
- * OST potently inhibited osteoclast differentiation and osteoclast-specific gene expression by suppressing the P38/MAPK and NF-κB pathways.
- * OST ameliorated LPS-induced bone resorption and modulated macrophage populations at osteolytic sites.
Conclusions:
- * Osthole (OST) exhibits significant anti-inflammatory and anti-osteolytic effects.
- * OST modulates macrophage polarization and inhibits osteoclastogenesis via the P38/MAPK and NF-κB pathways.
- * OST demonstrates considerable potential for the management of inflammatory lytic bone diseases.

