Tabersonine alleviates wear particle-induced inflammatory osteolysis by inhibiting osteoclast activation
- VernacularTitle:水甘草碱抑制破骨细胞活化缓解磨损颗粒诱导的炎性骨溶解
- Author:
Wei ZHANG
1
;
Lei YU
;
Peng YANG
;
Dechun GENG
Author Information
- Keywords: tabersonine; inflammatory factor; osteoclast activation; wear particle; periprosthetic osteolysis
- From: Chinese Journal of Tissue Engineering Research 2024;28(10):1519-1525
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Tabersonine has shown good therapeutic effects in diseases such as myocardial remodeling,acute kidney injury and lung injury due to its anti-inflammatory biological activity.Prosthetic wear particles often lead to aseptic inflammation,and the massive release of inflammatory factors further promotes periprosthetic bone destruction and bone loss;however,there are no basic studies on the efficacy of tabersonine on periprosthetic osteolysis. OBJECTIVE:To investigate the effects of tabersonine on osteoclast activation,expression of inflammatory factors and inflammatory osteolysis induced by wear particles. METHODS:(1)Cell experiment:RAW264.7 cells were divided into four groups for culture.A complete medium was added in the control group.Osteoclast induction medium(50 ng/mL RANKL+complete medium)was added to the osteoclast induction group.1 and 5 μmol/L tabersonine was added for 4 hours,and then osteoclast induction medium was added to the low-and high-dose tabersonine groups,respectively.After 5 days of induction,tartrate-resistant acid phosphatase staining,F-actin staining and RT-PCR were performed.(2)Animal experiments:Twenty C57BL/6J mice were randomly divided into sham operation group,osteolysis group,low-dose tabersonine group and high-dose tabersonine group(n=5 per group).Skull osteolysis model of the skull was established by injecting titanium pellets on the skull surface in the osteolysis group,low-dose tabersonine group and high-dose tabersonine group.On day 2 after model establishment,mice in the low-dose and high-dose tabersonine groups received intraperitoneal injections of 10 and 20 mg/kg tabersonine every 2 days,respectively.2 weeks after surgery,mouse sera were collected for detecting inflammatory factors(interleukin 1β,interleukin 6,and tumor necrosis factor α),and cranial bones were collected for micro-CT scan and bone parameter analysis. RESULTS AND CONCLUSION:(1)Cellular experiments:Tartrate-resistant acid phosphatase staining and F-actin staining showed that compared with the osteoclast induction group,low-dose and high-dose tabersonine significantly inhibited osteoclast activation and bone resorption,and the inhibition was more significant in the high-dose tabersonine group.RT-PCR results showed that compared with the control group,the mRNA expressions of three kinds of inflammatory factors were increased in the osteoclast induction group(P<0.01).Compared with the osteoclast induction group,the mRNA expressions of three kinds of inflammatory factors were decreased in low-and high-dose tabersonine groups(P<0.01),and the decrease was more obvious in the high-dose tabersonine group.(2)Animal experiments:Compared with the sham operation group,the levels of three kinds of inflammatory factors were increased in the osteolysis group(P<0.01).Compared with the osteolysis group,the levels of three kinds of inflammatory factors were decreased in the low-and high-dose tabersonine groups(P<0.05,P<0.01),and the decrease was more obvious in the high-dose tabersonine group.The micro-CT scan results revealed that titanium particles caused the destruction of cranial osteolysis,and tabersonine could inhibit the osteolysis induced by titanium particles,especially in the high-dose tabersonine group.(3)The results confirm that tabersonine can enhance the osteolysis and bone destruction induced by titanium particles by inhibiting the release of inflammatory factors and down-regulating the bone absorption function of osteoclasts.
