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Effects of 1,25-Dihydroxy vitamin D3 on TNF-α induced inflammation in human chondrocytes and SW1353 cells: a possible role for toll-like receptors

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The purpose of this study is to evaluate anti-inflammatory and chondro-protective effects of 1,25(OH)2D3 in human chondrocytes and SW1353 cells via investigating expressions of MMPs, TIMPs, VDR, and intracellular signalling pathway mediators such as TLR-2 and -4. The HC and SW1353 cells were treated with 1,25(OH)2D3 at 10, 100, and 1000 nM concentrations in the absence/presence of TNF-α (20 ng/mL) for 48 h. The mRNA expressions of MMP-1, -2, -3, -9, and -13, TIMP-1 and -2, VDR, TLR-2 and -4 in HC and SW1353 cells were detected by qPCR after treatments. The cytotoxicity and cell proliferation analyses were assessed by LDH and WST-1 assay, respectively. Protein levels of MMPs, TIMPs, and VDR were analysed by immunocytochemistry and ELISA methods. TNF-α markedly increased cytotoxicity for 24, 48, 72 h (p < 0.05) and vitamin D treatment was shown to diminish the cytotoxic effect of TNF-α. Cell proliferations increased by Vitamin D in a dose-dependent manner. mRNA expressions of MMP-1, -2, -3, -9, and -13, TLR-2 and -4 genes decreased with 1,25(OH)2D3 treatment (p < 0.05). VDR, TIMP-1 and -2 levels elevated after TNF-α exposure compared with the control group in HC cells (p < 0.05). Protein expression levels were determined using Western blotting, ELISA and immunocytochemistry. 1,25(OH)2D3 via binding to VDR, reversed the effects of TNF-α by inhibiting TLR-2 and 4. Decreased levels of VDR, TIMP-1 and -2 after TNF-α treatment were elevated by 1,25(OH)2D3 proportional with increasing 1,25(OH)2D3 doses. 1,25(OH)2D3 and TNF-α co-treatment decreased MMP-1, -2, -3, -9, and -13 levels were after TNF-α exposure.

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References

  1. Goldring MB (2006) Update on the biology of the chondrocyte and new approaches to treating cartilage diseases. Best Pract Res Clin Rheumatol 20(5):1003–1025

    Article  CAS  Google Scholar 

  2. Schuerwegh A, Dombrecht E, Stevens W, Van Offel J, Bridts C, De Clerck L (2003) Influence of pro-inflammatory (IL-1α, IL-6, TNF-α, IFN-γ) and anti-inflammatory (IL-4) cytokines on chondrocyte function. Osteoarthritis Cartilage 11(9):681–687

    Article  CAS  Google Scholar 

  3. Thomas JE, Bhat AK, Rao M, Guddattu V, Sekhar MS (2019) Use of vitamin D supplements in osteoarthritis: an observational study in a tertiary health care facility. J Am Coll Nutr 38(3):227–234

    Article  CAS  Google Scholar 

  4. Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, Zügel U, Steinmeyer A, Pollak A, Roth E (2006) Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol 36(2):361–370

    Article  CAS  Google Scholar 

  5. Castillo E, Hernandez-Cueto M, Vega-Lopez M, Lavalle C, Kouri J, Ortiz-Navarrete V (2012) Effects of vitamin D supplementation during the induction and progression of osteoarthritis in a rat model. Evid-Based Complement Altern Med 64:1697–1707

    Google Scholar 

  6. Kidd PM (2010) Vitamins D and K as pleiotropic nutrients: clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy. Altern Med Rev 15(3):199–222

    PubMed  Google Scholar 

  7. St-Arnaud R, Naja RP (2011) Vitamin D metabolism, cartilage and bone fracture repair. Mol Cell Endocrinol 347(1–2):48–54

    Article  CAS  Google Scholar 

  8. Hodge R, Mandle HB, Ray S, Tandon S, Peterson M, Henry A, Jahan FA, Bostick RM, Baron JA, Barry EL (2018) Effects of supplemental calcium and vitamin D on expression of toll-like receptors and phospho-IKKα/β in the normal rectal mucosa of colorectal adenoma patients. Cancer Prev Res 11(11):707–716

    Article  CAS  Google Scholar 

  9. López-López N, González-Curiel I, Treviño-Santa Cruz MB, Rivas-Santiago B, Trujillo-Paez V, Enciso-Moreno JA, Serrano CJ (2014) Expression and vitamin D-mediated regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in healthy skin and in diabetic foot ulcers. Arch Dermatol Res 306(9):809–821

    Article  Google Scholar 

  10. Dodge GR, Diaz A, Sanz-Rodriguez C, Reginato AM, Jimenez SA (1998) Effects of interferon-gamma and tumor necrosis factor alpha on the expression of the genes encoding aggrecan, biglycan, and decorin core proteins in cultured human chondrocytes. Arthritis Rheum 41(2):274–283. https://doi.org/10.1002/1529-0131(199802)41:2%3c274:aid-art11%3e3.0.co;2-z

    Article  CAS  PubMed  Google Scholar 

  11. Lin Z, Li W (2016) The roles of vitamin D and its analogs in inflammatory diseases. Curr Top Med Chem 16(11):1242–1261

    Article  CAS  Google Scholar 

  12. Guillot X, Semerano L, Saidenberg-Kermanach N, Falgarone G, Boissier M-C (2010) Vitamin D and inflammation. Joint Bone Spine 77(6):552–557

    Article  CAS  Google Scholar 

  13. Sassi F, Tamone C, D’Amelio P (2018) Vitamin D: nutrient, hormone, and immunomodulator. Nutrients 10(11):1656. https://doi.org/10.3390/nu10111656

    Article  CAS  PubMed Central  Google Scholar 

  14. Cantorna MT, Rogers CJ, Arora J (2019) Aligning the paradoxical role of vitamin D in gastrointestinal immunity. Trends Endocrinol Metab 30(7):459–466. https://doi.org/10.1016/j.tem.2019.04.005

    Article  CAS  PubMed  Google Scholar 

  15. Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M (2019) Randomized study of the effect of vitamin D and omega-3 fatty acids cosupplementation as adjuvant chemotherapy on inflammation and nutritional status in colorectal cancer patients. J Dietary Suppl. https://doi.org/10.1080/19390211.2019.1600096

    Article  Google Scholar 

  16. Hansen AK, Figenschau Y, Zubiaurre-Martinez I (2017) Co-expression of 1α-hydroxylase and vitamin D receptor in human articular chondrocytes. BMC Musculoskel Dis 18(1):432

    Article  Google Scholar 

  17. Alshahrani F, Aljohani N (2013) Vitamin D: deficiency, sufficiency and toxicity. Nutrients 5(9):3605–3616

    Article  Google Scholar 

  18. Stumpf WE, Koike N, Hayakawa N, Tokuda K, Nishimiya K, Tsuchiya Y, Hirate J, Okazaki A, Kumaki K (1994) 1,25-Dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3 in vivo nuclear receptor binding in developing bone during endochondral and intramembranous ossification. Histochemistry 102(3):183–194

    Article  CAS  Google Scholar 

  19. Wang Y, Zhu J, DeLuca HF (2014) Identification of the vitamin D receptor in osteoblasts and chondrocytes but not osteoclasts in mouse bone. J Bone Miner Res 29(3):685–692

    Article  CAS  Google Scholar 

  20. Carlberg C (2003) Current understanding of the function of the nuclear vitamin D receptor in response to its natural and synthetic ligands. In: Vitamin D Analogs in Cancer Prevention and Therapy. Springer, New York pp 29–42

    Google Scholar 

  21. Haussler MR, Haussler CA, Bartik L, Whitfield GK, Hsieh J-C, Slater S, Jurutka PW (2008) Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention. Nutr Rev 66(suppl_2):S98–S112

    Article  Google Scholar 

  22. Matilainen JM, Husso T, Toropainen S, Seuter S, Turunen MP, Gynther P, Ylä-Herttuala S, Carlberg C, Väisänen S (2010) Primary effect of 1α, 25 (OH) 2D3 on IL-10 expression in monocytes is short-term down-regulation. Biochem Biophys Acta 1803(11):1276–1286

    Article  CAS  Google Scholar 

  23. Dunlop TW, Väisänen S, Frank C, Carlberg C (2004) The genes of the coactivator TIF2 and the corepressor SMRT are primary 1α, 25 (OH) 2D3 targets. J Steroid Biochem Mol Biol 89:257–260

    Article  Google Scholar 

  24. Bai G, Howell D, Howard G, Roos B, Cheung H (2001) Basic calcium phosphate crystals up-regulate metalloproteinases but down-regulate tissue inhibitor of metalloproteinase-1 and-2 in human fibroblasts. Osteoarthritis Cartilage 9(5):416–422

    Article  CAS  Google Scholar 

  25. Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11(1):529–543

    Article  CAS  Google Scholar 

  26. Konttinen YT, Ainola M, Valleala H, Ma J, Ida H, Mandelin J, Kinne RW, Santavirta S, Sorsa T, López-Otín C (1999) Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis. Ann Rheum Dis 58(11):691–697

    Article  CAS  Google Scholar 

  27. Boyan B, Schwartz Z (2009) 1, 25-Dihydroxy vitamin D3 is an autocrine regulator of extracellular matrix turnover and growth factor release via ERp60-activated matrix vesicle matrix metalloproteinases. Cells Tissues Org 189(1–4):70–74

    Article  CAS  Google Scholar 

  28. Tetlow L, Woolley D (2001) Expression of vitamin D receptors and matrix metalloproteinases in osteoarthritic cartilage and human articular chondrocytes in vitro. Osteoarthritis Cartilage 9(5):423–431

    Article  CAS  Google Scholar 

  29. Meephansan J, Komine M, Tsuda H, Ohtsuki M (2012) Suppressive effect of calcipotriol on the induction of matrix metalloproteinase (MMP)-9 and MMP-13 in a human squamous cell carcinoma cell line. Clin Exp Dermatol 37(8):889–896

    Article  CAS  Google Scholar 

  30. Wang L-F, Tai C-F, Chien C-Y, Chiang F-Y, Chen JY-F (2015) Vitamin D decreases the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 in fibroblasts derived from Taiwanese patients with chronic rhinosinusitis with nasal polyposis. Kaohsiung J Med Sci 31(5):235–240

    Article  Google Scholar 

  31. Halder SK, Osteen KG, Al-Hendy A (2013) Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and-9 in human uterine fibroid cells. Hum Reprod 28(9):2407–2416

    Article  CAS  Google Scholar 

  32. Wang H, Zhang Q, Chai Y, Liu Y, Li F, Wang B, Zhu C, Cui J, Qu H, Zhu M (2015) 1,25(OH)2D3 downregulates the Toll-like receptor 4-mediated inflammatory pathway and ameliorates liver injury in diabetic rats. J Endocrinol Investig 38(10):1083–1091. https://doi.org/10.1007/s40618-015-0287-6

    Article  CAS  Google Scholar 

  33. Su SL, Tsai CD, Lee CH, Salter DM, Lee HS (2005) Expression and regulation of Toll-like receptor 2 by IL-1beta and fibronectin fragments in human articular chondrocytes. Osteoarthritis Cartilage 13(10):879–886. https://doi.org/10.1016/j.joca.2005.04.017

    Article  PubMed  Google Scholar 

  34. Di Rosa M, Malaguarnera G, De Gregorio C, Palumbo M, Nunnari G, Malaguarnera L (2012) Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages. Cell Immunol 280(1):36–43

    Article  Google Scholar 

  35. Gambhir V, Kim J, Siddiqui S, Taylor M, Byford V, Petrof EO, Jones G, Basta S (2011) Influence of 1,25-dihydroxy vitamin D3 on TLR4-induced activation of antigen presenting cells is dependent on the order of receptor engagement. Immunobiology 216(9):988–996. https://doi.org/10.1016/j.imbio.2011.03.011

    Article  CAS  PubMed  Google Scholar 

  36. Jiang J, Shi D, Zhou XQ, Yin L, Feng L, Jiang WD, Liu Y, Tang L, Wu P, Zhao Y (2015) Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus carpio var. Jian). Br J Nutr 114(10):1560–1568. https://doi.org/10.1017/s0007114515003256

    Article  CAS  PubMed  Google Scholar 

  37. Wells CA, Chalk AM, Forrest A, Taylor D, Waddell N, Schroder K, Himes SR, Faulkner G, Lo S, Kasukawa T (2006) Alternate transcription of the Toll-like receptor signaling cascade. Genome Biol 7(2):R10

    Article  Google Scholar 

  38. Do JE, Kwon SY, Park S, Lee E-S (2008) Effects of vitamin D on expression of Toll-like receptors of monocytes from patients with Behcet’s disease. Rheumatology 47(6):840–848

    Article  CAS  Google Scholar 

  39. Majumdar D, Frankiw L, Burns CH, Garcia-Flores Y, Baltimore D (2018) Programmed delayed splicing: a mechanism for timed inflammatory gene expression. bioRxiv:443796

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Acknowledgements

This research was supported by a Grant from the Scientific Research Projects, Project Number 3510, Center in Ankara Yildirim Beyazit University 2017.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Ankara Yildirim Beyazit University, 06800, Ankara, Turkey

    Gamze Avcioglu, Betül Özbek Ipteç, Gulsen Yilmaz & Leyla Didem Kozaci

  2. Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

    Ahmet Carhan

  3. Department of Histology and Embryology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

    Gülben Akcan

  4. Department of Translational Medicine, Institute of Health Sciences, Ankara Yildirim Beyazit University, Ankara, Turkey

    Büsra Görgün, Kübra Fidan, Ahmet Carhan, Gulsen Yilmaz & Leyla Didem Kozaci

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  1. Gamze Avcioglu
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Avcioglu, G., Özbek Ipteç, B., Akcan, G. et al. Effects of 1,25-Dihydroxy vitamin D3 on TNF-α induced inflammation in human chondrocytes and SW1353 cells: a possible role for toll-like receptors. Mol Cell Biochem 464, 131–142 (2020). https://doi.org/10.1007/s11010-019-03655-z

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