Tanshinone IIA attenuates polyethylene-induced osteolysis in a mouse model: The key role of miR-155-5p/FOXO3 axis

Abstract

• TAN has protective effects on knee tissues and osteoblasts against UHMWPE. • The anti-osteolysis effects of TAN depends on the induced level of miR-155-5p. • The induced level of miR-155-5p inhibited the function of FOXO3. • The inhibition of FOXO3 improved the balance between OPG and RANKL. Osteolysis is a major complication of total joint arthroplasty, and tanshinone IIA (TAN) can attenuate the disorder. The current study aimed to verify the anti-osteolysis potential of TAN and explore the associated mechanism. Osteolysis was induced in mice and in human hFoB 1.19 osteoblasts using ultrahigh molecular weight polyethylene (UHMWPE). The effects of TAN on joint tissue structure and inflammation and osteoblast viability, apoptosis, and inflammation were detected. The miR-155-5p level was modulated in osteoblasts to explain its role in the function of TAN. TAN attenuated UHMWPE-induced tissue destruction and suppressed inflammation. In the in vitro system, TAN increased cell viability, reduced cell apoptosis, and inhibited proinflammatory cytokines. TAN upregulated miR-155-5p and osteoprotegerin (OPG) and downregulated FOXO3 and RANKL. Once miR-155-5p was inhibited, the effects of TAN were counteracted. TAN exerted its anti-osteolysis effects by inducing miR-155-5p, which inhibited FOXO3 and balanced the levels of OPG and RANKL.