Advertisement

Calcified Tissue International

, Volume 105, Issue 6, pp 651–659 | Cite as

The Effect of Caffeine on Calcitriol-Inducible Vitamin D Receptor-Controlled Gene Expression in Intestinal and Osteoblastic Cells

  • Ondřej Ženata
  • Adéla Marcalíková
  • Radim VrzalEmail author
Original Research
  • 83 Downloads

Abstract

Some epidemiological studies suggested caffeine consumption as the cause for bone mineral density loss. Certain genes involved in this process are regulated by vitamin D receptor (VDR). Therefore, we investigated if caffeine can affect inducible expression of VDR-regulated genes, some of them being involved in bone mineralization process. By employing reporter gene assay, polymerase chain reaction, and western blotting, we monitored the VDR activity and expression in cell cultures of intestinal (LS180), osteosarcoma (HOS), and normal human osteoblasts in vitro. While caffeine stimulated calcitriol-inducible VDR-dependent nanoluciferase activity in stable reporter cell line IZ-VDRE (derived from LS180), it rather modulated mRNA levels of target genes, like CYP24A1, BGLAP, SPP1, and TNSF11 in LS180 and HOS cells. However, caffeine significantly decreased calcitriol-inducible CYP24A1, TNSF11, and SPP1 transcripts in osteoblasts. This decrease had non-linear U-shaped profile. Our in vitro data demonstrate biphasic action of caffeine on the expression of certain calcitriol-inducible VDR-regulated genes in normal human osteoblasts.

Keywords

Osteoblasts HOS IZ-VDRE BGLAP CYP24A1 SPP1 

Notes

Acknowledgements

This work was supported by the grant from Palacký University in Olomouc, PrF-2019-003.

Compliance with Ethical Standards

Conflict of interest

Ondrej Zenata, Adela Marcalikova, and Radim Vrzal declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human subjects performed by any of the authors.

References

  1. 1.
    Fulgoni VL 3rd, Keast DR, Lieberman HR (2015) Trends in intake and sources of caffeine in the diets of US adults: 2001-2010. Am J Clin Nutr 101(5):1081–1087CrossRefGoogle Scholar
  2. 2.
    Teekachunhatean S, Tosri N, Rojanasthien N, Srichairatanakool S, Sangdee C (2013) Pharmacokinetics of caffeine following a single administration of coffee enema versus oral coffee consumption in healthy male subjects. ISRN Pharmacol 2013:147238CrossRefGoogle Scholar
  3. 3.
    Chiang WF, Liao MT, Cheng CJ, Lin SH (2014) Rhabdomyolysis induced by excessive coffee drinking. Hum Exp Toxicol 33(8):878–881CrossRefGoogle Scholar
  4. 4.
    Jones AW (2017) Review of caffeine-related fatalities along with postmortem blood concentrations in 51 poisoning deaths. J Anal Toxicol 41(3):167–172CrossRefGoogle Scholar
  5. 5.
    Benowitz NL (1990) Clinical pharmacology of caffeine. Annu Rev Med 41:277–288CrossRefGoogle Scholar
  6. 6.
    Mediero A, Cronstein BN (2013) Adenosine and bone metabolism. Trends Endocrinol Metab: TEM 24(6):290–300CrossRefGoogle Scholar
  7. 7.
    Doepker C, Lieberman HR, Smith AP, Peck JD, El-Sohemy A, Welsh BT (2016) Caffeine: friend or foe? Annu Rev Food Sci Technol 7:117–137CrossRefGoogle Scholar
  8. 8.
    Hansen SA, Folsom AR, Kushi LH, Sellers TA (2000) Association of fractures with caffeine and alcohol in postmenopausal women: the Iowa Women’s Health Study. Public Health Nutr 3(3):253–261CrossRefGoogle Scholar
  9. 9.
    Hallstrom H, Wolk A, Glynn A, Michaelsson K (2006) Coffee, tea and caffeine consumption in relation to osteoporotic fracture risk in a cohort of Swedish women. Osteoporos Int 17(7):1055–1064CrossRefGoogle Scholar
  10. 10.
    Harter DL, Busnello FM, Dibi RP, Stein AT, Kato SK, Vanin CM (2013) Association between low bone mass and calcium and caffeine intake among perimenopausal women in Southern Brazil: cross-sectional study. Sao Paulo Med J = Rev Paul de Med 131(5):315–322CrossRefGoogle Scholar
  11. 11.
    Grainge MJ, Coupland CA, Cliffe SJ, Chilvers CE, Hosking DJ (1998) Cigarette smoking, alcohol and caffeine consumption, and bone mineral density in postmenopausal women. The Nottingham EPIC Study Group. Osteoporos Int 8(4):355–363CrossRefGoogle Scholar
  12. 12.
    Kerner SA, Scott RA, Pike JW (1989) Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D3. Proc Natl Acad Sci USA 86(12):4455–4459CrossRefGoogle Scholar
  13. 13.
    Mosavin R, Mellon WS (1996) Posttranscriptional regulation of osteocalcin mRNA in clonal osteoblast cells by 1,25-dihydroxyvitamin D3. Arch Biochem Biophys 332(1):142–152CrossRefGoogle Scholar
  14. 14.
    Neve A, Corrado A, Cantatore FP (2013) Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol 228(6):1149–1153CrossRefGoogle Scholar
  15. 15.
    Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER et al (1997) A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390(6656):175–179CrossRefGoogle Scholar
  16. 16.
    Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S et al (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95(7):3597–3602CrossRefGoogle Scholar
  17. 17.
    Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL (2001) Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 74(5):694–700CrossRefGoogle Scholar
  18. 18.
    Rapuri PB, Gallagher JC, Nawaz Z (2007) Caffeine decreases vitamin D receptor protein expression and 1,25(OH)2D3 stimulated alkaline phosphatase activity in human osteoblast cells. J Steroid Biochem Mol Biol 103(3–5):368–371CrossRefGoogle Scholar
  19. 19.
    Zenata O, Vrzal R (2017) Fine tuning of vitamin D receptor (VDR) activity by post-transcriptional and post-translational modifications. Oncotarget 8(21):35390–35402CrossRefGoogle Scholar
  20. 20.
    Bartonkova I, Grycova A, Dvorak Z (2016) Profiling of vitamin D metabolic intermediates toward VDR using novel stable gene reporter cell lines IZ-VDRE and IZ-CYP24. Chem Res Toxicol 29(7):1211–1222CrossRefGoogle Scholar
  21. 21.
    Zenata O, Dvorak Z, Vrzal R (2018) Mycophenolate Mofetil induces c-Jun-N-terminal kinase expression in 22Rv1 cells: an impact on androgen receptor signaling. J Cancer 9(11):1915–1924CrossRefGoogle Scholar
  22. 22.
    Doricakova A, Theile D, Weiss J, Vrzal R (2017) Differential effects of the enantiomers of tamsulosin and tolterodine on P-glycoprotein and cytochrome P450 3A4. Naunyn-Schmiedeberg’s Arch Pharmacol 390(1):49–59CrossRefGoogle Scholar
  23. 23.
    Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C et al (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397(6717):315–323CrossRefGoogle Scholar
  24. 24.
    Su SJ, Chang KL, Su SH, Yeh YT, Shyu HW, Chen KM (2013) Caffeine regulates osteogenic differentiation and mineralization of primary adipose-derived stem cells and a bone marrow stromal cell line. Int J Food Sci Nutr 64(4):429–436CrossRefGoogle Scholar
  25. 25.
    Clemente N, Raineri D, Cappellano G, Boggio E, Favero F, Soluri MF et al (2016) Osteopontin bridging innate and adaptive immunity in autoimmune diseases. J Immunol Res 2016:7675437Google Scholar
  26. 26.
    Ferrari S, Rizzoli R, Manen D, Slosman D, Bonjour JP (1998) Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3’-end region polymorphisms. J Bone Miner Research: Off J Am Soc Bone Miner Res 13(6):925–930CrossRefGoogle Scholar
  27. 27.
    Garnero P, Munoz F, Borel O, Sornay-Rendu E, Delmas PD (2005) Vitamin D receptor gene polymorphisms are associated with the risk of fractures in postmenopausal women, independently of bone mineral density. J Clin Endocrinol Metab 90(8):4829–4835CrossRefGoogle Scholar
  28. 28.
    Fang Y, van Meurs JB, d’Alesio A, Jhamai M, Zhao H, Rivadeneira F et al (2005) Promoter and 3’-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the rotterdam study. Am J Hum Genet 77(5):807–823CrossRefGoogle Scholar
  29. 29.
    Jurutka PW, Remus LS, Whitfield GK, Thompson PD, Hsieh JC, Zitzer H et al (2000) The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB. Mol Endocrinol 14(3):401–420CrossRefGoogle Scholar
  30. 30.
    Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M (2003) Effects of caffeine on human health. Food Addit Contam 20(1):1–30CrossRefGoogle Scholar
  31. 31.
    Harris SS, Dawson-Hughes B (1994) Caffeine and bone loss in healthy postmenopausal women. Am J Clin Nutr 60(4):573–578CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Cell Biology and Genetics, Faculty of SciencePalacky University in OlomoucOlomoucCzech Republic

Personalised recommendations