AB0802 Effects of dietary magnesium supplementation and intra-articular magnesium sulfate on experimental osteoarthritis and potential molecular mechanisms by mrna and lncrna expression profiles screening
Authors: G Lei, C Zeng, H Li, J Wei, T Yang, B Wise, X Ding, Y Zhang, Y Yang, Z Deng, J Li, Y Cui
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Epidemiological studies of ours and other groups have reported an inverse association between dietary and serum Mg with knee radiographic osteoarthritis (OA) [1–4]. <h3>Objectives</h3> To investigate the effects of dietary magnesium supplementation and intra-articular MgSO<sub>4</sub> on the development of experimental rat osteoarthritis, and explore the underlying potential molecular mechanisms by mRNA and lncRNA expression profiles screening. <h3>Methods</h3> Rat osteoarthritis model was induced by surgery. Articular cartilage damage was evaluated by modified Mankin score system after intervention of dietary magnesium supplementation or intra-articular MgSO<sub>4</sub> injection. Microarray was performed to reveal alteration of expression profiles of mRNA and lncRNA after intervention of MgSO<sub>4</sub> on human osteoarthritis chondrocytes. Bioinformatics analyses including gene ontology analysis, pathway analysis, target gene predictions and network analysis were used. <h3>Results</h3> Comparing with normal diet, dietary Mg supplementation showed significantly ameliorated cartilage damage at the medial femoral condyle, lateral tibial plateau and medial tibial plateau (P≤0.05), and approaching significance at the lateral femoral condyle (P=0.06). All four locations exhibited mitigated cartilage damage in the intra-articular MgSO<sub>4</sub> group compared with intra-articular saline (P≤0.05). 1767 lncRNAs and 2558 mRNAs were upregulated while 994 lncRNAs and 1512 mRNAs were downregulated in chondrocytes with intervention of 50mM MgSO4 compared with control group (fold change ≥2.0). The top 6 lncRNAs which showed the largest difference were ENST00000425914.2, ENST00000419881.1, ENST00000561231.1, ENST00000609062.1, TCONS_00029212 and ENST00000429530.1. Bioinformatics analyses indicated that the differentially expressed lncRNA target genes of chondrocyte after intervention of 50mM MgSO<sub>4</sub> are enriched in negative regulation of phosphatidylinositol 3-kinase signaling. <h3>Conclusions</h3> Both dietary magnesium supplementation and intra-articular MgSO<sub>4</sub> injection may exert cartilage protective effects by causing widespread changes in the profile of lncRNAs and mRNAs of chondrocytes. <h3>References</h3> Hunter DJ. Evidence of altered bone turnover, vitamin D and calcium regulation with knee osteoarthritis in female twins. Rheumatology 2003;42(11):1311–6. Zeng C, Wei J, Li H, Yang T, Zhang FJ, Pan D, et al. Relationship between Serum Magnesium Concentration and Radiographic Knee Osteoarthritis. J Rheumatol 2015;42(7):1231–6. Qin B, Shi X, Samai PS, Renner JB, Jordan JM, He K. Association of dietary magnesium intake with radiographic knee osteoarthritis: Results from a population-based study. Arthritis Care &amp; Research 2012;64(9):1306–11. Zeng C, Li H, Wei J, Yang T, Deng Z, Yang Y, et al. Association between Dietary Magnesium Intake and Radiographic Knee Osteoarthritis. PLOS ONE 2015;10(5):e127666. <h3>Disclosure of Interest</h3> None declared