title: 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.
authors.affiliation: Department of Joint Surgery, Tianjin Hospital, 406 Jiefang South Road, Hexi District, Tianjin 300211, P.R. China.
authors.forename: De-Zhi
authors.initials: DZ
authors.lastname: Zheng
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Bu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation; D006023:Glycoproteins / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010014:Osteolysis / Q000188:drug therapy* / Q000235:genetics; D015854:Up-Regulation; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D000099274:Frizzled-Related Proteins; C582652:MIRN130 microRNA, mouse
keywords: FRZB; Osteolysis; Wear particles; miR-130b