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.

Key words: tabersonine, inflammatory factor, osteoclast activation, wear particle, periprosthetic osteolysis