Project description:Aseptic loosening in total joint replacement due to insufficient osteointegration is an unsolved problem in orthopaedics.The purpose of our study was to obtain a picture of the initial protein adsorption layer on femoral endoprosthetic surfaces as the key to the initiation of osseointegration.
Project description:Aseptic loosening represents a significant factor contributing to joint replacement failure, primarily associated with diminished bone formation and heightened osteoclast-induced osteolysis. Here, a natural polymer-based injectable hydrogel that encapsulates irisin protein (referred to as I-OG hydrogel) is reported. The hierarchical cross-linked structure of the I-OG hydrogel confers favorable mechanical properties, desirable self-healing ability, and acceptable injectability and, more importantly, sustains continuous release of the protein at the interface between the bone and implant prosthesis. The I-OG hydrogel effectively fills the gap between the titanium pin and bone tissue, successfully inhibiting aseptic loosening induced by titanium particles, which outcome confirms the occurrence of irisin protein's slow-release process and its inhibitory effect on osteolysis. Mechanistically, our in vitro experiments demonstrated that irisin released from the I-OG hydrogel upregulates the Wnt/β-catenin signaling pathway in bone marrow stromal cells (BMSCs) through integrin αV, while concurrently downregulating the NF-κB (P65) signaling pathway in osteoblasts. These molecular events ultimately promote osteogenic differentiation and inhibit osteoclast activation. Collectively, our findings establish that the I-OG hydrogel effectively counteracts aseptic loosening by resisting osteolysis caused by titanium particles and enhancing periprosthetic bone formation, and offers promising prospects for the treatment of aseptic loosening in prosthetic implants.
Project description:In 21 patients undergoing revision arthroplasty due to septic or aseptic implant loosening, synovial fluid was collected intraoperatively after opening the joint capsule. In a proteomic MS approach, we wanted now to investigate these synovial fluids for novel proteogenic markers of periprosthetic infections.
Project description:Unilateral femoral artery occlusion (right side) and a sham operation on the contralateral (left) side was performed in C57BL/6J mice under anesthesia by double ligation of the superficial femoral artery proximal to the deep femoral artery and distal femoral artery. Animal numbers are stated with the different experimental results. Total RNA was isolated from the distal adductor muscles by phenol-chloroform isolation (TRIzol, Invitrogen, Carlsbad, CA) at baseline and at 5 time points after femoral artery ligation (6h, 24h, 3 days, 7 days, 14 days) from 5 mice per time point. RNA was pooled in equal amounts, and microarray analysis for all identified murine miRNAs (miRBase 9.0) was performed by a service provider (LC Sciences, Houston, TX).
Project description:Unilateral femoral artery occlusion (right side) and a sham operation on the contralateral (left) side was performed in C57BL/6J mice under anesthesia by double ligation of the superficial femoral artery proximal to the deep femoral artery and distal femoral artery. Animal numbers are stated with the different experimental results. Total RNA was isolated from the distal adductor muscles by phenol-chloroform isolation (TRIzol, Invitrogen, Carlsbad, CA) at baseline and at 5 time points after femoral artery ligation (6h, 24h, 3 days, 7 days, 14 days) from 5 mice per time point. RNA was pooled in equal amounts, and microarray analysis for all identified murine miRNAs (miRBase 9.0) was performed by a service provider (LC Sciences, Houston, TX). 11 condition experiment. Biological replicates: 5 per condition, 5 pooled RNA replicates per array.
Project description:Increasing evidence has demonstrated that circular RNA exerts important function in the pathogenesis of some diseases. While, the contributions of circRNAs to aseptic lossening after total hip arthroplasty remain largely unknown. Our research is to explore the differently expressed circRNAs and elucidate complex regulated mechanism of circRNAs in aseptic lossening. The differently expressed circRNAs were identified by RNA sequencing analysis. Reverse transcription-quantitative polymerase chain reaction was adopted to corroborate these differently expressed circRNAs. The potential function of circRNAs in aseptic lossening tissue was identified by competing endogenous RNA analysis. Enrichment analysis were performed for target mRNAs and host genes of the differently expressed circRNAs by Gene Oncology and Kyoto Encyclopedia of Genes and Genomes. 257 differently expressed circRNAs were obtained from RNA-seq results. Then, circRNA–miRNA–mRNA network was established based on the validated circRNAs. The result of Gene Oncology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the circRNAs were related with some biological functions and pathways of aseptic lossening. A novel pathogenesis and treatment strategy about aseptic lossening after total hip arthroplasty was revealed from our study of circRNA–miRNA–mRNA network.