MicroRNA-130b Promotes Wear Particle-Induced Osteolysis via Downregulating Frizzled-Related Protein (FRZB).

Abstract

Periprosthetic osteolysis induced by wear particles can lead to aseptic loosening, one main reason of arthroplasty failure. However, the role of microRNA-130b (miR-130b) in particle-induced osteolysis (PIO) has not been explored yet. In this study, PIO models were established in C57BL/J6 mice via the implantation of Co-Cr-Mo alloy particles, and evaluated by detecting tartrate-resistant acid phosphatase (TRAP) activity and bone resorption in the calvaria. Mouse preosteoblast MC3T3-E1 cells were cultured to receive particle stimulation in vitro. Real time PCR and western blotting were performed to determine the expression levels of miR-130b and frizzled-related protein (FRZB), one potential target of miR-130b. Results showed upregulated miR-130b and downregulated FRZB in both PIO mice with remarkable osteolysis and particle-treated MC3T3-E1 cells showing inhibited proliferation and differentiation assayed by bromodeoxy urodine (BrdU) incorporation and alkaline phosphatase (ALP) activity respectively. Functional studies were conducted by transfection of miR-130b inhibitor in vitro or the injections of miR-130b inhibitor or small interfering RNA (siRNA) targeting FRZB in vivo. Interestingly, particle-induced inhibition on cell proliferation, differentiation and FRZB expression were all reversed by miR-130b silence. Luciferase report assays demonstrated that miR-130b indeed negatively regulated FRZB expression by targeting, while FRZB could reverse the opposed effect of miR-130b silence on PIO development. Therefore, the upregulated miR-130b in PIO models could act as one key regulator of PIO development, partly due to its negative regulation on FRZB.