Research Article
BibTex RIS Cite

The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts

Year 2021, Volume: 14 Issue: 2, 217 - 224, 30.06.2021

Tayfun Dikmen

https://doi.org/10.30607/kvj.889086

Abstract

Bone metabolism is a complicated and challenging issue in both physiological and pathological states. The homeostasis of the tissue is majorly being managed by the competing activities of osteoblasts and osteoclasts. Osteoprotegerin (OPG) is a decoy receptor for RANKL and it inhibits osteoclast differentiation by binding RANKL and being produced primarily by osteoblasts. The decrease in OPG level causes excessive osteoclast activation which results in high bone resorption that overcomes new bone formation. Therefore, it is important to understand the mechanism of OPG production and identify its regulators. In this study, it was aimed to address the effects of TGF-ß3, 17-ß estradiol and bisphenol A (BPA), an endocrine disrupter, on OPG production from osteoblasts. For this purpose, hfOB cells were treated with TGF-ß3, 17-ß estradiol and BPA for 48 hours both alone and in combinations. The effects of these agents were evaluated by sandwich-ELISA. The analysis showed that TGF-ß3 and 17-ß estradiol treatment causes an increase in OPG levels when used in combination. It was also discovered that BPA exhibits antagonistic effect on OPG production when used along with TGF-ß3 and 17-ß estradiol.

Keywords

17-ß Estradiol Bisphenol A Osteoprotegerin TGF-ß3

Thanks

The author would like to express his deep gratitude to Prof. Dr. Korhan ALTUNBAŞ and Asst. Prof. Dr. Özlem ÖZDEN AKKAYA for reviewing the manuscript.

References

  • Bouillon R, Suda T. Vitamin D: calcium and bone homeostasis during evolution. Bonekey Rep. Nature Publishing Group; 2014;3(January): 1–10. http://dx.doi.org/10.1038/bonekey.2013.214
  • Chaparro A, Sanz A, Wolnitzky A, Realini O, Bendek MJ, Betancur D, Albers D, Beltrán V. Lymphocyte b and th17 chemotactic cytokine levels in peri-implant crevicular fluid of patients with healthy, peri-mucositis, and peri-implantitis implants. J. Oral Res. 2020;2020(Special Issue 1): 20–5.
  • Diel P, Schulz T, Smolnikar K, Strunck E, Vollmer G, Michna H. Ability of xeno- and phytoestrogens to modulate expression of estrogen-sensitive genes in rat uterus: Estrogenicity profiles and uterotropic activity. J. Steroid Biochem. Mol. Biol. 2000;73(1–2): 1–10.
  • Dougall WC. Mechanistic role of RANKL in cancer-induced bone diseases and development of a targeted therapy to inhibit this pathway [Internet]. First edit. Bone Cancer. Elsevier Inc.; 2010. http://dx.doi.org/10.1016/B978-0-12-374895-9.00032-3
  • Foo C, Frey S, Yang HH, Zellweger R, Filgueira L. Downregulation of β-catenin and transdifferentiation of human osteoblasts to adipocytes under estrogen deficiency. Gynecol. Endocrinol. 2007;23(9): 535–40.
  • Grafe I, Alexander S, Peterson JR, Snider TN, Levi B, Lee B, Mishina Y. TGF-β Family Signaling in Mesenchymal Differentiation. Cold Spring Harb. Perspect. Biol. Cold Spring Harbor Laboratory Press; 2018;10(5): a022202. https://pubmed.ncbi.nlm.nih.gov/28507020
  • HIROI H, TSUTSUMI O, MOMOEDA M, TAKAI Y, OSUGA Y, TAKETANI Y. Differential Interactions of Bisphenol A and17β-estradiol with Estrogen Receptor α (ERα) and ERβ Endocr. J. 1999;46(6): 773–8.
  • Hofbauer LC, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines. Biochem. Biophys. Res. Commun. 1998;250(3): 776–81.
  • Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL. Estrogen Stimulates Gene Expression and Protein Production of Osteoprotegerin in Human Osteoblastic Cells*. Endocrinology. 1999;140(9): 4367–70. https://doi.org/10.1210/endo.140.9.7131
  • Hong LIU, Colpan A, Peptan IA. Differentiations of Human Mesenchymal Stem Cells. 2006;12(10).
  • Hwang JK, Min KH, Choi KH, Hwang YC, Jeong IK, Ahn KJ, Chung HY, Chang JS. Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts. Life Sci. Elsevier Inc.; 2013;93(9–11): 367–72. http://dx.doi.org/10.1016/j.lfs.2013.07.020
  • Jing J, Pu Y, Gingrich J, Veiga-Lopez A. Gestational Exposure to Bisphenol A and Bisphenol S Leads to Fetal Skeletal Muscle Hypertrophy Independent of Sex. Toxicol. Sci. 2019;172(2): 292–302.
  • Karbanodvá J, Soukup T, Suchánek J, Mokrý J. Osteogenic differentiation of human dental pulp-derived stem cells under various ex-vivo culture conditions. Acta Medica (Hradec Kralove). 2010;53(2): 79–84.
  • Katagiri T, Takahashi N. Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis. 2002;8(3): 147–59.
  • Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux NY, Goncalves RB, Valverde P, Dibart S, Li YP, Miranda LA, Ernst CWO, Izumi Y, Taubman MA. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am. J. Pathol. American Society for Investigative Pathology; 2006;169(3): 987–98. http://dx.doi.org/10.2353/ajpath.2006.060180
  • Köttstorfer J, Thomas A, Gregori M, Kecht M, Kaiser G, Eipeldauer S, Sarahrudi K. Are OPG and RANKL involved in human fracture healing? J. Orthop. Res. 2014;32(12): 1557–61.
  • Lam J, Teitelbaum SL, Fremont DH, Lam J, Nelson CA, Ross FP, Teitelbaum SL, Fremont DH. Crystal structure of the TRANCE / RANKL cytokine reveals determinants of receptor- ligand specificity Find the latest version : Crystal structure of the Online first publication TRANCE / RANKL cytokine reveals determinants of receptor-ligand specificity. 2001;108(7): 971–9.
  • Langdahl B, Ferrari S, Dempster DW. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis. Ther. Adv. Musculoskelet. Dis. 2016;8(6): 225–35.
  • McClung M. Role of RANKL inhibition in osteoporosis. Arthritis Res. Ther. 2007;9(SUPPL.1): 1–6.
  • Murakami T, Yamamoto M, Yamamoto M, Ono K, Nishikawa M, Nagata N, Motoyoshi K, Akatsu T. Transforming growth factor-β1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells. Biochem. Biophys. Res. Commun. 1998;252(3): 747–52.
  • Özden Akkaya Ö, Yağcı A, Tosun M, Altunbaş K. Fötal ve Neonatal Rat Beyin Dokusunda Bisphenol A’nın Notch Sinyal Yolağı Üzerine Etkisi. Uludağ Üniversitesi Vet. Fakültesi Derg. 2018;37(2): 109–17.
  • Rodan GA. Commentary Bone homeostasis. Commentary. 1998;95(November): 13361–2.
  • Routledge EJ, White R, Parker MG, Sumpter JP. Differential effects of xenoestrogens on coactivator recruitment by estrogen receptor (ER) α and ERβ. J. Biol. Chem. 2000;275(46): 35986–93.
  • Saika M, Inoue D, Kido S, Matsumoto T. 17β-Estradiol Stimulates Expression of Osteoprotegerin by a Mouse Stromal Cell Line, ST-2, via Estrogen Receptor-α*. Endocrinology 2001;142(6): 2205–12. https://doi.org/10.1210/endo.142.6.8220
  • Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: Paracrine regulators of bone metabolism and vascular function. Arterioscler. Thromb. Vasc. Biol. 2002;22(4): 549–53.
  • Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trall G, Sullivan J, … Boyle WJ. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2): 309–19.
  • Thent ZC, Froemming GRA, Muid S. Bisphenol A exposure disturbs the bone metabolism: An evolving interest towards an old culprit. Life Sci. Elsevier Inc; 2018;198(2017): 1–7. https://doi.org/10.1016/j.lfs.2018.02.013
  • Thent ZC, Ruth Anisah Froemming G, Binti Mohd Ismail A, Baharom Syed Ahmad Fuad S, Muid S. Phytoestrogens by inhibiting the non-classical oestrogen receptor, overcome the adverse effect of bisphenol A on hFOB 1.19 cells. Iran. J. Basic Med. Sci. 2020;23(9): 1155–63.
  • Thirunavukkarasu K, Miles RR, Halladay DL, Yang X, Galvin RJS, Chandrasekhar S, Martin TJ, Onyia JE. Stimulation of osteoprotegerin (OPG) gene expression by transforming growth factor-β (TGF-β). Mapping of the OPG promoter region that mediates TGF-β effects. J. Biol. Chem. 2001;276(39): 36241–50.
  • Tong X, Gu J, Song R, Wang D, Sun Z, Sui C, Zhang C, Liu X, Bian J, Liu Z. Osteoprotegerin inhibit osteoclast differentiation and bone resorption by enhancing autophagy via AMPK/mTOR/p70S6K signaling pathway in vitro. J. Cell. Biochem. 2019;120(2): 1630–42.
  • Udagawa N, Takahashi N, Akatsu T, Tanaka H, Sasaki T, Nishihara T, Koga T, Martin TJ, Suda T. Origin of osteoclasts: Mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc. Natl. Acad. Sci. U. S. A. 1990;87(18): 7260–4.
  • Vitku-Kubatova J, Kolatorova L, Franekova L, Blahos J, Simkova M, Duskova M, Skodova T, Starka L. Endocrine disruptors of the bisphenol and paraben families and bone metabolism. Physiol. Res. 2018;67: S455–64.
  • Wang Q, Yu J hua, Zhai H hong, Zhao Q tao, Chen J wu, Shu L, Li D qiang, Liu D yong, dong C, Ding Y. Temporal expression of estrogen receptor alpha in rat bone marrow mesenchymal stem cells. Biochem. Biophys. Res. Commun. 2006;347(1): 117–23.
  • Yen M, Chien C-C, Chiu I, Huang H-I, Chen Y-C, Hu H-I, Yen BL. Multilineage Differentiation and Characterization of the Human Fetal Osteoblastic 1.19 Cell Line: A Possible In Vitro Model of Human Mesenchymal Progenitors. Stem Cells. 2007;25(1): 125–31.
  • Yeo L, Toellner KM, Salmon M, Filer A, Buckley CD, Raza K, Scheel-Toellner D. Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann. Rheum. Dis. 2011;70(11): 2022–8.
  • Zuo HL, Xin H, Yan XN, Huang J, Zhang YP, Du H. 17β-Estradiol improves osteoblastic cell function through the Sirt1/NF-κB/MMP-8 pathway. Climacteric. 2020;23(4): 404–9.

TGF-ß3, 17-ß Estradiol ve Bisphenol A’nın Osteoblastlar Üzerinde Osteoprotegerin Üretimine Etkileri

Year 2021, Volume: 14 Issue: 2, 217 - 224, 30.06.2021

Tayfun Dikmen

https://doi.org/10.30607/kvj.889086

Abstract

Kemik metabolizması hem fizyolojik hem de patolojik durumlarda karmaşık ve zorlu bir konudur. Dokunun homeostazisi büyük oranda osteoblastların ve osteoklastların karşılıklı aktiviteleri ile idare edilmektedir. Osteoprotegerin (OPG), başlıca osteoblastlar tarafından üretilen ve RANKL ile bağlanarak osteoklast farklılaşmasının inhibe edilmesini sağlayan bir tuzak reseptördür. OPG seviyesindeki düşüş yoğun osteoklast aktivasyonuna ve dolayısı ile yeni kemik yapımını aşan miktarda kemik yıkımına sebep olmaktadır. Bu nedenle OPG üretim mekanizmasını anlamak ve OPG’nin düzenleyicilerini identifiye etmek önem arz etmektedir. Bu çalışmada TGF-ß3, 17-ß estradiol ve bir endokrin bozucu olan bisfenol A’nın (BPA) osteoblastlardan OPG üretimine etkilerinin belirlenmesi amaçlandı. Bu amaçla hfOB hücrelerine TGF-ß3, 17-ß estradiol ve BPA 48 saat boyunca tek başlarına ve kombinasyon halinde uygulandı. Bu faktörlerin etkileri sandviç ELISA yöntemi ile değerlendirildi. Yapılan analizde TGF-ß3 ve 17-ß estradiolün kombinasyon halinde kullanımının OPG seviyelerinde artış sağladığı belirlendi. Ayrıca, çalışmada BPA’nın OPG üretimi üzerine antagonistik etkilerini TGF-ß3 ve 17-ß estradiol ile birlikte uygulandığında gösterdiği gözlendi.

Keywords

Bisphenol A 17-ß Estradiol TGF-ß3 Osteoprotegerin

References

  • Bouillon R, Suda T. Vitamin D: calcium and bone homeostasis during evolution. Bonekey Rep. Nature Publishing Group; 2014;3(January): 1–10. http://dx.doi.org/10.1038/bonekey.2013.214
  • Chaparro A, Sanz A, Wolnitzky A, Realini O, Bendek MJ, Betancur D, Albers D, Beltrán V. Lymphocyte b and th17 chemotactic cytokine levels in peri-implant crevicular fluid of patients with healthy, peri-mucositis, and peri-implantitis implants. J. Oral Res. 2020;2020(Special Issue 1): 20–5.
  • Diel P, Schulz T, Smolnikar K, Strunck E, Vollmer G, Michna H. Ability of xeno- and phytoestrogens to modulate expression of estrogen-sensitive genes in rat uterus: Estrogenicity profiles and uterotropic activity. J. Steroid Biochem. Mol. Biol. 2000;73(1–2): 1–10.
  • Dougall WC. Mechanistic role of RANKL in cancer-induced bone diseases and development of a targeted therapy to inhibit this pathway [Internet]. First edit. Bone Cancer. Elsevier Inc.; 2010. http://dx.doi.org/10.1016/B978-0-12-374895-9.00032-3
  • Foo C, Frey S, Yang HH, Zellweger R, Filgueira L. Downregulation of β-catenin and transdifferentiation of human osteoblasts to adipocytes under estrogen deficiency. Gynecol. Endocrinol. 2007;23(9): 535–40.
  • Grafe I, Alexander S, Peterson JR, Snider TN, Levi B, Lee B, Mishina Y. TGF-β Family Signaling in Mesenchymal Differentiation. Cold Spring Harb. Perspect. Biol. Cold Spring Harbor Laboratory Press; 2018;10(5): a022202. https://pubmed.ncbi.nlm.nih.gov/28507020
  • HIROI H, TSUTSUMI O, MOMOEDA M, TAKAI Y, OSUGA Y, TAKETANI Y. Differential Interactions of Bisphenol A and17β-estradiol with Estrogen Receptor α (ERα) and ERβ Endocr. J. 1999;46(6): 773–8.
  • Hofbauer LC, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines. Biochem. Biophys. Res. Commun. 1998;250(3): 776–81.
  • Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL. Estrogen Stimulates Gene Expression and Protein Production of Osteoprotegerin in Human Osteoblastic Cells*. Endocrinology. 1999;140(9): 4367–70. https://doi.org/10.1210/endo.140.9.7131
  • Hong LIU, Colpan A, Peptan IA. Differentiations of Human Mesenchymal Stem Cells. 2006;12(10).
  • Hwang JK, Min KH, Choi KH, Hwang YC, Jeong IK, Ahn KJ, Chung HY, Chang JS. Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts. Life Sci. Elsevier Inc.; 2013;93(9–11): 367–72. http://dx.doi.org/10.1016/j.lfs.2013.07.020
  • Jing J, Pu Y, Gingrich J, Veiga-Lopez A. Gestational Exposure to Bisphenol A and Bisphenol S Leads to Fetal Skeletal Muscle Hypertrophy Independent of Sex. Toxicol. Sci. 2019;172(2): 292–302.
  • Karbanodvá J, Soukup T, Suchánek J, Mokrý J. Osteogenic differentiation of human dental pulp-derived stem cells under various ex-vivo culture conditions. Acta Medica (Hradec Kralove). 2010;53(2): 79–84.
  • Katagiri T, Takahashi N. Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis. 2002;8(3): 147–59.
  • Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux NY, Goncalves RB, Valverde P, Dibart S, Li YP, Miranda LA, Ernst CWO, Izumi Y, Taubman MA. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am. J. Pathol. American Society for Investigative Pathology; 2006;169(3): 987–98. http://dx.doi.org/10.2353/ajpath.2006.060180
  • Köttstorfer J, Thomas A, Gregori M, Kecht M, Kaiser G, Eipeldauer S, Sarahrudi K. Are OPG and RANKL involved in human fracture healing? J. Orthop. Res. 2014;32(12): 1557–61.
  • Lam J, Teitelbaum SL, Fremont DH, Lam J, Nelson CA, Ross FP, Teitelbaum SL, Fremont DH. Crystal structure of the TRANCE / RANKL cytokine reveals determinants of receptor- ligand specificity Find the latest version : Crystal structure of the Online first publication TRANCE / RANKL cytokine reveals determinants of receptor-ligand specificity. 2001;108(7): 971–9.
  • Langdahl B, Ferrari S, Dempster DW. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis. Ther. Adv. Musculoskelet. Dis. 2016;8(6): 225–35.
  • McClung M. Role of RANKL inhibition in osteoporosis. Arthritis Res. Ther. 2007;9(SUPPL.1): 1–6.
  • Murakami T, Yamamoto M, Yamamoto M, Ono K, Nishikawa M, Nagata N, Motoyoshi K, Akatsu T. Transforming growth factor-β1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells. Biochem. Biophys. Res. Commun. 1998;252(3): 747–52.
  • Özden Akkaya Ö, Yağcı A, Tosun M, Altunbaş K. Fötal ve Neonatal Rat Beyin Dokusunda Bisphenol A’nın Notch Sinyal Yolağı Üzerine Etkisi. Uludağ Üniversitesi Vet. Fakültesi Derg. 2018;37(2): 109–17.
  • Rodan GA. Commentary Bone homeostasis. Commentary. 1998;95(November): 13361–2.
  • Routledge EJ, White R, Parker MG, Sumpter JP. Differential effects of xenoestrogens on coactivator recruitment by estrogen receptor (ER) α and ERβ. J. Biol. Chem. 2000;275(46): 35986–93.
  • Saika M, Inoue D, Kido S, Matsumoto T. 17β-Estradiol Stimulates Expression of Osteoprotegerin by a Mouse Stromal Cell Line, ST-2, via Estrogen Receptor-α*. Endocrinology 2001;142(6): 2205–12. https://doi.org/10.1210/endo.142.6.8220
  • Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: Paracrine regulators of bone metabolism and vascular function. Arterioscler. Thromb. Vasc. Biol. 2002;22(4): 549–53.
  • Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trall G, Sullivan J, … Boyle WJ. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2): 309–19.
  • Thent ZC, Froemming GRA, Muid S. Bisphenol A exposure disturbs the bone metabolism: An evolving interest towards an old culprit. Life Sci. Elsevier Inc; 2018;198(2017): 1–7. https://doi.org/10.1016/j.lfs.2018.02.013
  • Thent ZC, Ruth Anisah Froemming G, Binti Mohd Ismail A, Baharom Syed Ahmad Fuad S, Muid S. Phytoestrogens by inhibiting the non-classical oestrogen receptor, overcome the adverse effect of bisphenol A on hFOB 1.19 cells. Iran. J. Basic Med. Sci. 2020;23(9): 1155–63.
  • Thirunavukkarasu K, Miles RR, Halladay DL, Yang X, Galvin RJS, Chandrasekhar S, Martin TJ, Onyia JE. Stimulation of osteoprotegerin (OPG) gene expression by transforming growth factor-β (TGF-β). Mapping of the OPG promoter region that mediates TGF-β effects. J. Biol. Chem. 2001;276(39): 36241–50.
  • Tong X, Gu J, Song R, Wang D, Sun Z, Sui C, Zhang C, Liu X, Bian J, Liu Z. Osteoprotegerin inhibit osteoclast differentiation and bone resorption by enhancing autophagy via AMPK/mTOR/p70S6K signaling pathway in vitro. J. Cell. Biochem. 2019;120(2): 1630–42.
  • Udagawa N, Takahashi N, Akatsu T, Tanaka H, Sasaki T, Nishihara T, Koga T, Martin TJ, Suda T. Origin of osteoclasts: Mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc. Natl. Acad. Sci. U. S. A. 1990;87(18): 7260–4.
  • Vitku-Kubatova J, Kolatorova L, Franekova L, Blahos J, Simkova M, Duskova M, Skodova T, Starka L. Endocrine disruptors of the bisphenol and paraben families and bone metabolism. Physiol. Res. 2018;67: S455–64.
  • Wang Q, Yu J hua, Zhai H hong, Zhao Q tao, Chen J wu, Shu L, Li D qiang, Liu D yong, dong C, Ding Y. Temporal expression of estrogen receptor alpha in rat bone marrow mesenchymal stem cells. Biochem. Biophys. Res. Commun. 2006;347(1): 117–23.
  • Yen M, Chien C-C, Chiu I, Huang H-I, Chen Y-C, Hu H-I, Yen BL. Multilineage Differentiation and Characterization of the Human Fetal Osteoblastic 1.19 Cell Line: A Possible In Vitro Model of Human Mesenchymal Progenitors. Stem Cells. 2007;25(1): 125–31.
  • Yeo L, Toellner KM, Salmon M, Filer A, Buckley CD, Raza K, Scheel-Toellner D. Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann. Rheum. Dis. 2011;70(11): 2022–8.
  • Zuo HL, Xin H, Yan XN, Huang J, Zhang YP, Du H. 17β-Estradiol improves osteoblastic cell function through the Sirt1/NF-κB/MMP-8 pathway. Climacteric. 2020;23(4): 404–9.
There are 36 citations in total.

Details

Primary Language English
Subjects Veterinary Surgery
Journal Section RESEARCH ARTICLE
Authors

Tayfun Dikmen 0000-0003-4470-7465

Publication Date June 30, 2021
Acceptance Date April 6, 2021
Published in Issue Year 2021 Volume: 14 Issue: 2

Cite

APA Dikmen, T. (2021). The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts. Kocatepe Veterinary Journal, 14(2), 217-224. https://doi.org/10.30607/kvj.889086
AMA Dikmen T. The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts. kvj. June 2021;14(2):217-224. doi:10.30607/kvj.889086
Chicago Dikmen, Tayfun. “The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts”. Kocatepe Veterinary Journal 14, no. 2 (June 2021): 217-24. https://doi.org/10.30607/kvj.889086.
EndNote Dikmen T (June 1, 2021) The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts. Kocatepe Veterinary Journal 14 2 217–224.
IEEE T. Dikmen, “The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts”, kvj, vol. 14, no. 2, pp. 217–224, 2021, doi: 10.30607/kvj.889086.
ISNAD Dikmen, Tayfun. “The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts”. Kocatepe Veterinary Journal 14/2 (June 2021), 217-224. https://doi.org/10.30607/kvj.889086.
JAMA Dikmen T. The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts. kvj. 2021;14:217–224.
MLA Dikmen, Tayfun. “The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts”. Kocatepe Veterinary Journal, vol. 14, no. 2, 2021, pp. 217-24, doi:10.30607/kvj.889086.
Vancouver Dikmen T. The Effects of TGF-ß3, 17-ß Estradiol and Bisphenol A on Osteoprotegerin Production in Osteoblasts. kvj. 2021;14(2):217-24.
 Download Cover Image

13520    13521       13522   1352314104

14105         14106        14107       14108