4.6 Article

Transcriptomic changes in porcine articular cartilage one year following disruption of the anterior cruciate ligament

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PLOS ONE
卷 18, 期 5, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0284777

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In order to study the transcriptomic changes during early- to mid-stage posttraumatic osteoarthritis (PTOA) development, 72 Yucatan minipigs underwent transection of the anterior cruciate ligament. The subjects were divided into three groups: no further intervention, ligament reconstruction, or ligament repair. The gene expression analysis showed that there was an initial increase in transcriptomic differences at 1 and 4 weeks followed by a stark reduction at 52 weeks. Different treatments were found to genetically modulate the course of PTOA. Specific genes were identified as being upregulated in the cartilage of injured subjects across all timepoints, and certain genes that have not been associated with PTOA before were found to be differentially expressed at the 52-week timepoint.
To determine the transcriptomic changes seen in early- to mid-stage posttraumatic osteoarthritis (PTOA) development, 72 Yucatan minipigs underwent transection of the anterior cruciate ligament. Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair, followed by articular cartilage harvesting and RNA-sequencing at three different postoperative timepoints (1, 4, and 52 weeks). Six additional subjects received no ligament transection and provided cartilage tissue to serve as controls. Differential gene expression analysis between post-transection cartilage and healthy cartilage revealed an initial increase in transcriptomic differences at 1 and 4 weeks followed by a stark reduction in transcriptomic differences at 52 weeks. This analysis also showed how different treatments genetically modulate the course of PTOA following ligament disruption. Specific genes (e.g., MMP1, POSTN, IGF1, PTGFR, HK1) were identified as being upregulated in the cartilage of injured subjects across all timepoints regardless of treatment. At the 52-week timepoint, 4 genes (e.g., A4GALT, EFS, NPTXR, ABCA3) that-as far as we know-have yet to be associated with PTOA were identified as being concordantly differentially expressed across all treatment groups when compared to controls. Functional pathway analysis of injured subject cartilage compared to control cartilage revealed overarching patterns of cellular proliferation at 1 week, angiogenesis, ECM interaction, focal adhesion, and cellular migration at 4 weeks, and calcium signaling, immune system activation, GABA signaling, and HIF-1 signaling at 52 weeks.

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