Tanshinone IIA protects against polyethylene particle-induced osteolysis response in a mouse calvarial model

The expression of beta-catenin in detectable aseptic loosening after joint replacement and the surrounding osteolysis of the prosthesis is primarily caused by the abrasive particles introduced by the prosthesis, which results in a shortened service life of the prosthesis. Recent studies have shown that debris can induce many cytokines associated with osteolysis. In particular, RANKL directly stimulates osteoclast formation and activity. Thus, we hypothesize that the osteolysis induced by wear particles can be prevented by inhibiting the RANKL signaling pathway. In this study, we established a C57BL/J6 mouse calvarial model of PE granule induced osteolysis, and studied the inhibitory action of tanshinone IIA on osteoclast formation. Eight-week-old male c57BL/J6 mouse were randomly divided into four groups: Sham group (no PE particle-induced + PBS), positive group (PE particle-inducted + PBS), low dose group (PE particle-induced + 1 ug/g tanshinone IIA), and high-dose group (PE granule-induced + 2 ug/g tanshinone II). After 21 days, the mice were executed and the calvaria were collected and processed for micro-CT scan and histomorphometry analysis. Compared to the positive subgroup, Tanshinone IIA significantly reduced bone absorption induced by PE granules and inhibited the formation and activity of osteoclasts. In addition, ELISA test showed that tanshinone IIA significantly reduced OSCAR and CTX-1 expression. Further, tanshinone IIA enhanced the formation of OPG, thus reducing osteoclast damage to the bone around the implant. Overall, these data indicate that tanshinone IIA represents a promising drug for the treatment of bone absorption by particles and can be a new method of treatment for prophylaxis of aseptic loosening.