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Echinacoside Inhibits Osteoclast Function by Down-Regulating PI3K/Akt/C-Fos to Alleviate Osteolysis Caused by
Tao Jiang1,2, Hanwen Gu2, Jian Wei1
1Department of Joint Orthopedics, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.
Abstract:
Infected osteolysis as a common secondary osteoporosis is associated with excessive osteoclastogenesis and bone resorption. The inhibition of osteoclastogenesis and bone resorption have been demonstrated an effective approach in the treatment of osteolytic diseases. Echinacoside (ECH) is a natural phenylethanoid glycoside with multiple biological functions, including anti-inflammatory, antioxidant, and osteoblast differentiation promotion. However, the effects of ECH on osteoclast differentiation and bone resorption function remain unknown. In vitro, we investigated the effects of ECH on osteoclast differentiation and bone resorption induced by RANKL and its potential mechanisms. In vivo, we established a periprosthetic joint infection (PJI) rat model and demonstrated the changes of infected osteolysis and osteoclasts activities in surgical sites. ECH (20 mg/kg) was injected intraperitoneally after debridement for 4 weeks. Radiological evaluation and bone histomorphometric analysis was performed to assess the efficacy of ECH. The results showed that ECH inhibited osteoclast differentiation, F-actin belts formation, bone resorption function and osteoclast-specific gene expression by preventing NFATc1 translocation, down-regulating its expression and affecting the PI3K/Akt/c-Fos pathway in vitro. ECH also alleviated in vivo PJI-induced osteolysis and maintained bone mass by inhibiting osteoclast activity. Our study indicated that ECH attenuated RANKL-induced osteoclastogenesis and PJI-induced bone loss and was shown as a potentially effective therapeutic agent for osteoclast-related bone diseases.
Insights
Echinacoside (ECH) effectively inhibits osteoclast formation and bone resorption in infected osteolysis models. This natural compound shows promise for treating bone diseases driven by excessive osteoclast activity.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Infected osteolysis, a complication of osteoporosis, involves excessive osteoclast activity and bone loss.
- Inhibiting osteoclastogenesis is a key strategy for treating osteolytic diseases.
- Echinacoside (ECH), a natural compound, has known anti-inflammatory and antioxidant properties, but its effect on osteoclasts is unexplored.
Purpose of the Study:
- To investigate the effects of Echinacoside (ECH) on osteoclast differentiation and bone resorption.
- To elucidate the underlying mechanisms of ECH's action on osteoclasts.
- To evaluate ECH's therapeutic potential in a rat model of periprosthetic joint infection (PJI)-induced osteolysis.
Main Methods:
- In vitro studies assessed ECH's impact on osteoclast differentiation and bone resorption induced by RANKL.
- In vivo experiments utilized a PJI rat model to evaluate ECH's efficacy in treating infected osteolysis.
- Key molecular pathways, including NFATc1 translocation and the PI3K/Akt/c-Fos pathway, were analyzed.
Main Results:
- ECH significantly inhibited osteoclast differentiation, F-actin belt formation, and bone resorption in vitro.
- ECH prevented NFATc1 translocation and down-regulated osteoclast-specific gene expression by affecting the PI3K/Akt/c-Fos pathway.
- In vivo, ECH treatment alleviated PJI-induced osteolysis, preserved bone mass, and reduced osteoclast activity.
Conclusions:
- Echinacoside (ECH) effectively suppresses RANKL-induced osteoclastogenesis and PJI-induced bone loss.
- ECH demonstrates potential as a therapeutic agent for osteoclast-related bone diseases.
- ECH's mechanism involves inhibiting NFATc1 translocation and modulating the PI3K/Akt/c-Fos pathway.
