Selenomethionine against titanium particle-induced osteolysis by regulating the ROS-dependent NLRP3 inflammasome activation via the β-catenin signaling pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA993111 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25213461_1.fastq.gz | Fastqsanger.gz | |||
| SRR25213461_2.fastq.gz | Fastqsanger.gz | |||
| SRR25213462_1.fastq.gz | Fastqsanger.gz | |||
| SRR25213462_2.fastq.gz | Fastqsanger.gz | |||
| SRR25213463_1.fastq.gz | Fastqsanger.gz |
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Project description:Wear debris-induced osteolysis, especially titanium (Ti) particles-induced osteolysis, is the most common cause of arthroplasty failure with no effective therapy. Previous studies have suggested that inflammation and impaired osteogenesis are associated with Ti particles -induced osteolysis. Selenium (Se) is an essential trace element in the human body, which forms selenomethionine (Se-Met) in nature, and selenoproteins has strong anti-inflammatory and antioxidant stress effects. In this study, the effects of Se-Met on Ti particles-induced osteolysis were observed and the potential mechanism was explored. We found that exogenous Se-Met relieved osteolysis induced by Ti particles in two animal models and MC3T3-E1 cells. We found that the addition of Se-Met effectively inhibited Ti particle-induced inflammation by regulating ROS-dependent NLRP3 inflammasome activation. These therapeutic effects were abrogated in MC3T3-E1 cells that had received a β-catenin antagonist, suggesting that Se-Met alleviates inflammatory osteolysis via the β-catenin signaling pathway. Collectively, these findings indicated that Se-Met may serve as a potential therapeutic agent for treating Ti particle-induced osteolysis.
2023-08-09 | GSE236911 | GEO
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.
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Project description:Wear debris-induced osteolysis, especially titanium (Ti) particles-induced osteolysis, is the most common cause of arthroplasty failure with no effective therapy. Previous studies have suggested that inflammation and impaired osteogenesis are associated with Ti particles -induced osteolysis. Selenium (Se) is an essential trace element in the human body, which forms selenomethionine (Se-Met) in nature, and selenoproteins has strong anti-inflammatory and antioxidant stress effects. In this study, the effects of Se-Met on Ti particles-induced osteolysis were observed and the potential mechanism was explored. We found that exogenous Se-Met relieved osteolysis induced by Ti particles in two animal models and MC3T3-E1 cells. We found that the addition of Se-Met effectively inhibited Ti particle-induced inflammation by regulating reactive oxygen species-dependent (ROS-dependent) NOD-like receptor protein 3 (NLRP3) inflammasome activation. These therapeutic effects were abrogated in MC3T3-E1 cells that had received a β-catenin antagonist, suggesting that Se-Met alleviates inflammatory osteolysis via the β-catenin signaling pathway. Collectively, these findings indicated that Se-Met may serve as a potential therapeutic agent for treating Ti particle-induced osteolysis.
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