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Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1β-stimulated human osteoarthritis chondrocytes: potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5

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Abstract

Purpose

MicroRNAs (miRNAs) are short, non-coding RNAs involved in almost all cellular processes. Epigallocatechin-3-O-gallate (EGCG) is a green tea polyphenol and is known to exert anti-arthritic effects by inhibiting genes associated with osteoarthritis (OA). This study was undertaken to investigate the global effect of EGCG on interleukin-1β (IL-1β)-induced expression of miRNAs in human chondrocytes.

Methods

Human chondrocytes were derived from OA cartilage and then treated with EGCG and IL-1β. Human miRNA microarray technology was used to determine the expression profile of 1347 miRNAs. Microarray results were verified by taqman assays and transfection of chondrocytes with miRNA inhibitors.

Results

Out of 1347 miRNAs, EGCG up-regulated expression of 19 miRNAs and down-regulated expression of 17 miRNAs, whereas expression of 1311 miRNAs remains unchanged in IL-1β-stimulated human OA chondrocytes. Bioinformatics approach showed that 3`UTR of ADAMTS5 mRNA contains the ‘seed-matched-sequence’ for hsa-miR-140-3p. IL-1β-induced expression of ADAMTS5 correlated with down-regulation of hsa-miR-140-3p. Importantly, EGCG inhibited IL-1β-induced ADAMTS5 expression and up-regulated the expression of hsa-miR-140-3p. This EGCG-induced co-regulation between ADAMTS5 and hsa-miR-140-3p becomes reversed in OA chondrocytes transfected with anti-miR-140-3p.

Conclusions

This study provides an important insight into the molecular basis of the reported anti-arthritic effects of EGCG. Our data indicate that the potential of EGCG in OA chondrocytes may be related to its ability to globally inhibit inflammatory response via modulation of miRNAs expressions.

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References

  1. Troeberg L, Nagase H (2012) Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim Biophys Acta 1824:133–145

    Article  CAS  Google Scholar 

  2. Apte SS (2016) Anti-ADAMTS5 monoclonal antibodies: implications for aggrecanase inhibition in osteoarthritis. Biochem J 473:e1–e4

    Article  CAS  Google Scholar 

  3. Huang K, Wu LD (2008) Aggrecanase and aggrecan degradation in osteoarthritis: a review. J Int Med Res 36:1149–1160

    Article  CAS  Google Scholar 

  4. Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA (2005) Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 434:644–648

    Article  CAS  Google Scholar 

  5. Glasson SS, Askew R, Sheppard B, Carito BA, Blanchet T, Ma HL, Flannery CR, Kanki K, Wang E, Peluso D, Yang Z, Majumdar MK, Morris EA (2004) Characterization of and osteoarthritis susceptibility in ADAMTS-4-knockout mice. Arthritis Rheum 50:2547–2558

    Article  CAS  Google Scholar 

  6. Pasquinelli AE (2012) MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 13:271–282

    Article  CAS  Google Scholar 

  7. Lovendorf MB, Skov L (2015) Epigenetics and dermatology. Chapter 9—MicroRNAs in skin diseases. pp 177–205

  8. Sondag GR, Haqqi TM (2016) The role of microRNAs and their targets in osteoarthritis. Curr Rheumatol Rep 18:56

    Article  Google Scholar 

  9. Mirzamohammadi F, Papaioannou G, Kobayashi T (2014) MicroRNAs in cartilage development, homeostasis, and disease. Curr Osteoporos Rep 12:410–419

    Article  Google Scholar 

  10. Kobayashi T, Lu J, Cobb BS, Rodda SJ, McMahon AP, Schipani E, Merkenschlager M, Kronenberg HM (2008) Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc Natl Acad Sci USA 105:1949–1954

    Article  CAS  Google Scholar 

  11. Miyaki S, Sato T, Inoue A, Otsuki S, Ito Y, Yokoyama S, Kato Y, Takemoto F, Nakasa T, Yamashita S, Takada S, Lotz MK, Ueno-Kudo H, Asahara H (2010) MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev 24:1173–1185

    Article  CAS  Google Scholar 

  12. Rasheed Z, Al-Shobaili HA, Rasheed N, Al Salloom AA, Al-Shaya O, Mahmood A, Alajez NM, Alghamdi AS, Mehana EE (2016) Integrated study of globally expressed microRNAs in IL-1β-stimulated human osteoarthritis chondrocytes and osteoarthritis relevant genes: a microarray and bioinformatics analysis. Nucleosides Nucleotides Nucleic Acids 35:335–355

    Article  CAS  Google Scholar 

  13. Akhtar N, Rasheed Z, Ramamurthy S, Anbazhagan AN, Voss FR, Haqqi TM (2010) MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes. Arthritis Rheum 62:1361–1371

    Article  CAS  Google Scholar 

  14. Rasheed Z, Al-Shobaili HA, Rasheed N, Mahmood A, Khan MI (2016) MicroRNA-26a-5p regulates the expression of inducible nitric oxide synthase via activation of NF-κB pathway in human osteoarthritis chondrocytes. Arch Biochem Biophys 594:61–67

    Article  CAS  Google Scholar 

  15. Meng F, Zhang Z, Chen W, Huang G, He A, Hou C, Long Y, Yang Z, Zhang Z, Liao W (2016) MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1β-induced chondrocyte responses. Osteoarthritis Cartilage 24:932–941

    Article  CAS  Google Scholar 

  16. Hou C, Meng F, Zhang Z, Kang Y, Chen W, Huang G, Fu M, Sheng P, Zhang Z, Liao W (2015) The role of MICRORNA-381 in chondrogenesis and interleukin-1-β induced chondrocyte responses. Cell Physiol Biochem 36:1753–1766

    Article  CAS  Google Scholar 

  17. Makki MS, Haseeb A, Haqqi TM (2015) MicroRNA-9 promotion of interleukin-6 expression by inhibiting monocyte chemoattractant protein-induced protein 1 expression in interleukin-1β-stimulated human chondrocytes. Arthritis Rheumatol 67:2117–2128.

    Article  CAS  Google Scholar 

  18. Akhtar N, Makki MS, Haqqi TM (2015) MicroRNA-602 and microRNA-608 regulate sonic hedgehog expression via target sites in the coding region in human chondrocytes. Arthritis Rheumatol 67:423–434.

    Article  CAS  Google Scholar 

  19. Park SJ, Cheon EJ, Lee MH, Kim HA (2013) MicroRNA-127-5p regulates matrix metalloproteinase 13 expression and interleukin-1β-induced catabolic effects in human chondrocytes. Arthritis Rheum 65:3141–3152

    Article  CAS  Google Scholar 

  20. Park SJ, Cheon EJ, Kim HA (2013) MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes. Osteoarthritis Cartilage 21:981–989

    Article  CAS  Google Scholar 

  21. Rasheed Z (2016) Green tea bioactive polyphenol epigallocatechin-3-o-gallate in osteoarthritis: current status and future perspectives. Int J Health Sci (Qassim) 10:V-VIII.

  22. Haqqi TM, Anthony DD, Gupta S, Ahmad N, Lee MS, Kumar GK, Mukhtar H (1999) Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl Acad Sci USA 96:4524–4529

    Article  CAS  Google Scholar 

  23. Akhtar N, Haqqi TM (2011) Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes. Arthritis Res Ther 13:R93

    Article  CAS  Google Scholar 

  24. Singh R, Akhtar N, Haqqi TM (2010) Green tea polyphenol epigallocatechin-3-gallate: inflammation and arthritis. Life Sci 86:907–918

    Article  CAS  Google Scholar 

  25. Ahmed S, Wang N, Lalonde M, Goldberg VM, Haqqi TM (2004) Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits interleukin-1 beta-induced expression of matrix metalloproteinase-1 and—13 in human chondrocytes. J Pharmacol Exp Ther 308:767–773

    Article  CAS  Google Scholar 

  26. Ahmed S, Rahman A, Hasnain A, Lalonde M, Goldberg VM, Haqqi TM (2002) Green tea polyphenol epigallocatechin-3-gallate inhibits the IL-1 beta-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes. Free Radic Biol Med 33:1097–1105

    Article  CAS  Google Scholar 

  27. Rasheed Z, Anbazhagan AN, Akhtar N, Ramamurthy S, Voss FR, Haqqi TM (2009) Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes. Arthritis Res Ther 11:R71

    Article  Google Scholar 

  28. Zhu K, Wang W (2016) Green tea polyphenol EGCG suppresses osteosarcoma cell growth through upregulating miR-1. Tumour Biol 37:4373–4382

    Article  CAS  Google Scholar 

  29. Sethi S, Li Y, Sarkar FH (2013) Regulating miRNA by natural agents as a new strategy for cancer treatment. Curr Drug Targets 14:1167–1174

    Article  CAS  Google Scholar 

  30. Tsang WP, Kwok TT (2010) Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells. J Nutr Biochem 21:140–146

    Article  CAS  Google Scholar 

  31. Jiang L, Tao C, He A, He X (2014) Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate. World J Surg Oncol 12:383

    Article  Google Scholar 

  32. Yamada S, Tsukamoto S, Huang Y, Makio A, Kumazoe M, Yamashita S, Tachibana H (2016) Epigallocatechin-3-O-gallate up-regulates microRNA-let-7b expression by activating 67-kDa laminin receptor signaling in melanoma cells. Sci Rep 6:19225.

    Article  CAS  Google Scholar 

  33. Rasheed Z, Rasheed N, Al-Shobaili HA (2016) Epigallocatechin-3-O-gallate up-regulates microRNA-199a-3p expression by down-regulating the expression of cyclooxygenase-2 in stimulated human osteoarthritis chondrocytes. J Cell Mol Med 20:2241–2248

    Article  CAS  Google Scholar 

  34. Rasheed Z, Haqqi TM (2012) Endoplasmic reticulum stress induces the expression of COX-2 through activation of eIF2α, p38-MAPK and NF-κB in advanced glycation end products stimulated human chondrocytes. Biochim Biophys Acta 1823:2179–2189

    Article  CAS  Google Scholar 

  35. Rasheed Z, Akhtar N, Haqqi TM (2011) Advanced glycation end products induce the expression of interleukin-6 and interleukin-8 by receptor for advanced glycation end product-mediated activation of mitogen-activated protein kinases and nuclear factor-κB in human osteoarthritis chondrocytes. Rheumatology (Oxford) 50:838–851

    Article  CAS  Google Scholar 

  36. Rasheed Z, Akhtar N, Haqqi TM (2010) Pomegranate extract inhibits the interleukin-1β-induced activation of MKK-3, p38α-MAPK and transcription factor RUNX-2 in human osteoarthritis chondrocytes. Arthritis Res Ther 12:R195

    Article  Google Scholar 

  37. Agarwal V, Bell GW, Nam JW, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. Elife Aug 12;4.

  38. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45

    Article  CAS  Google Scholar 

  39. Qureshi HY, Ahmad R, Zafarullah M (2008) High-efficiency transfection of nucleic acids by the modified calcium phosphate precipitation method in chondrocytes. Anal Biochem 382:138–140

    Article  CAS  Google Scholar 

  40. Miyaki S, Nakasa T, Otsuki S, Grogan SP, Higashiyama R, Inoue A, Kato Y, Sato T, Lotz MK, Asahara H (2009) MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses. Arthritis Rheum 60:2723–2730

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Science, Technology and Innovation Plan (NSTIP) Grant #11-BIO1885-09 from Qassim University, KSA. Support from Professor Hani A. Al-Shobaili (Dean, College of Medicine, Qassim University, KSA) is acknowledged and greatly appreciated.

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Authors and Affiliations

  1. Department of Medical Biochemistry, College of Medicine, Qassim University, P.O. Box 6655, Buraidah, 51452, Saudi Arabia

    Zafar Rasheed & Naila Rasheed

  2. Department of Orthopedics, King Fahd Medical City, Riyadh, Saudi Arabia

    Osama Al-Shaya

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  1. Zafar Rasheed
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  2. Naila Rasheed
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  3. Osama Al-Shaya
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Correspondence to Zafar Rasheed.

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Rasheed, Z., Rasheed, N. & Al-Shaya, O. Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1β-stimulated human osteoarthritis chondrocytes: potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5. Eur J Nutr 57, 917–928 (2018). https://doi.org/10.1007/s00394-016-1375-x

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  • DOI: https://doi.org/10.1007/s00394-016-1375-x

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