Magnesium supplementation modifies synovial and splenic transcriptomic signatures and biologic pathways in arthritis mice
Rheumatoid arthritis (RA) is a common chronic autoimmune and inflammatory disease that can cause joint pain and disability. We have recently reported that oral magnesium supplementation significantly reduces disease severity and joint damage in two models of RA. In the synovial tissues. There was an enrichment for differentially expressed genes (DEGs) belonging to pathways implicated in transcription regulation, nuclear receptor signaling, and pathways implicated in RA pathogenesis such as RHO GTPases, RUNX1 pathway, oxidative stress induced senescence, senescence-associated secretory phenotype (SASP) and cell migration in synovial tissues . In the synovial tissues Actc1 and Nr4a3 were among the genes with the highest expression, while Krt79 and Ffar2 were among the genes with the most significantly decreased expression in Mg2800 group compared with Mg500. Spleens had an enrichment for Metabolism of folate and pterines, HSP90 chaperone cycle for steroid hormone receptor. Syt5 and Hspa1a were among the genes with the highest expression, while Ano2 and Ascl4 were among the genes with the lowest expression levels in spleens from Mg2800 compared with Mg500. We describe the tissue transcriptomic consequences of the arthritis-protecting increased Mg dietary intake in KSIA mice. These results show that oral Mg supplementation may interfere with pathways implicated response to oxidative stress and senescence, and other processes known to participate in RA pathogenesis. Our findings provide new evidence supporting the disease-suppressing effect of increased Mg intake in arthritis. Oral Mg supplementation has the potential to become a new addition to the therapeutic options for RA and other autoimmune and inflammatory diseases. Overall design: In the present study we analyze the transcriptome of spleens and synovial tissues obtained from mice with KRN serum induced arthritis (KSIA) in either the Mg supplemented diet (Mg2800; n=5) or the normal diet (Mg500; n=5). Tissues were collected at the end of a 15-day KSIA experiment. RNA was purified and used for RNA sequencing, and groups compared using DESq2 R package, followed by pathway analyses using Reactome and Gene Ontology (GO).