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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
  1. G Lei1,
  2. C Zeng1,
  3. H Li1,
  4. J Wei2,
  5. T Yang1,
  6. B Wise3,
  7. X Ding1,
  8. Y Zhang1,
  9. Y Yang1,
  10. Z Deng1,
  11. J Li4,
  12. Y Cui5
  1. 1Department of Orthopaedics
  2. 2Health Management Center, Xiangya Hospital of Central South University, Changsha, Hunan Province, China
  3. 3Department of Internal Medicine and Department of Orthopaedics, University of California, Davis School of Medicine, Sacramento, CA
  4. 4Division of Rheumatology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States
  5. 5International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan Province, China

Abstract

Background Epidemiological studies of ours and other groups have reported an inverse association between dietary and serum Mg with knee radiographic osteoarthritis (OA) [1–4].

Objectives To investigate the effects of dietary magnesium supplementation and intra-articular MgSO4 on the development of experimental rat osteoarthritis, and explore the underlying potential molecular mechanisms by mRNA and lncRNA expression profiles screening.

Methods 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 MgSO4 injection. Microarray was performed to reveal alteration of expression profiles of mRNA and lncRNA after intervention of MgSO4 on human osteoarthritis chondrocytes. Bioinformatics analyses including gene ontology analysis, pathway analysis, target gene predictions and network analysis were used.

Results 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 MgSO4 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 MgSO4 are enriched in negative regulation of phosphatidylinositol 3-kinase signaling.

Conclusions Both dietary magnesium supplementation and intra-articular MgSO4 injection may exert cartilage protective effects by causing widespread changes in the profile of lncRNAs and mRNAs of chondrocytes.

References

  1. Hunter DJ. Evidence of altered bone turnover, vitamin D and calcium regulation with knee osteoarthritis in female twins. Rheumatology 2003;42(11):1311–6.

  2. 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.

  3. 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 & Research 2012;64(9):1306–11.

  4. 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.

References

Disclosure of Interest None declared

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