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Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

ABSTRACT: We report an immortalised CRISPR-Cas9 mesenchymal stem cell line knockdown of Plectin, we initally noted that patients with osteoarthritis association single nucelotide polymorphism rs11780978 had a correlation between genotype at rs11780978 and allelic expression imbalance, with a reduced expression of Plectin from the risk allele. We replicated the effect of the risk allele by deleting 26bp from exon 3 of Plectin to generate multiple knockdown lines to assess the molecular phenotype of Plectin knockdown in the cells. Our data suggest that Plectin knockdown was detectable in the RNA-sequencing data but at a significantly lower level compared to control. The knock-down was very efficient at the protein level, with a near total absence of plectin observed. The knock-down impacted on a range of cellular pathways. Of particular note, both the innate and the acquired immune response showed an upregulation, an effect that has been reported on previously in OA for both cartilage and synovium . Downregulation of Wnt signalling was also of interest, as this pathway is critical to cartilage homeostasis. Furthermore, there is growing evidence of an interplay between Wnt signalling and inflammation in joint tissues.

ORGANISM(S): Homo sapiens

PROVIDER: GSE143725 | GEO | 2020/07/07

REPOSITORIES: GEO

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