Taurine Activates BMP-2/Wnt3a-Mediated Osteoblast Differentiation and Mineralization via Akt and MAPK Signaling
Abstract
Background: We aimed to elucidate the preventive effects of taurine against osteopenia in ovariectomized (OVX) rats and the mechanisms by which taurine regulates osteoblastogenesis in vitro and in vivo.
Methods: The effects of the taurine on human osteoblast MG-63 cell differentiation and osteoblastogenesis effect in OVX rat were examined Konkuk University in 2018 by evaluating osteoblast differentiation, and expression of osteoblast-specific factors by western blotting analysis.
Results: Taurine supplementation significantly improved alkaline phosphatase (ALP) activity and mineralization in a concentration-dependent manner. Further, taurine induced the expression of osteogenic growth factors such as bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (RUNX2), small mothers against decapentaplegic 1/5/8 (SMAD1/5/8), wingless-type MMTV integration site family member 3A (Wnt3a), and collagen type 1 (COL-1) via mitogen-activated protein kinase (MAPK) and serine/threonine protein kinase (Akt). Moreover, the RUNX2 activity of the taurine-treated group was enhanced by protein-protein interactions such as Wnt3a-induced p-AKT/RUNX2 and BMP-mediated SMADs/MAPK/RUNX2 interactions.
Conclusion: Our in vitro and in vivo results suggested that taurine can be considered as a potential therapeutic candidate agent for preventing bone loss in postmenopausal osteoporosis.
1. Khan A, Fortier M, Reid R et al (2014). Osteoporosis in monopause. J Obstet Gynaecol Can, 36(9):839-840.
2. Young DR, Niklowitz WJ, Brown RJ et al (1986). Immobilization-associated osteoporosis in primates. Bone, 7(2):109-117.
3. Hollenbach KA, Barrett-Connor E, Edel-stein SL et al (1993). Cigarette Smoking and Bone Mineral Density in Older Men and Women. Am J Public Health, 83(9):1265-1270.
4. Maurel DB, Boisseau N, Benhamou CL et al (2012). Alcohol and bone, review of dose effects and mechanisms. Osteoporos Int, 23(1):1-16.
5. Jang HD, Hong JY, Han K et al (2017). Relationship between bone mineral density and alcohol intake: A nationwide health survey analysis of postmenopausal women. PLoS One, 29;12(6):e0180132.
6. Shams-White MM, Chung M, Du M et al (2017). Dietary protein and bone health, a systematic review and meta-analysis from the National Osteoporosis Foundation. Am J Clin Nutr, 105(6):1528-1543.
7. Huxtable RJ (1992). Physiological Actions of Taurine. Physiol Rev, 72(1):101-63.
8. Yuan LQ, Xie H, Luo XH et al (2006). Taurine transporter is expressed in osteoblasts. Amino Acids, 31(2):157-163.
9. Murakami S (2015). Role of taurine in the pathogenesis of obesity. Mol Nutr Food Res, 59(7):1353-1363.
10. Cheong SH, Moon SH, Lee SJ et al (2013). Antioxidant and DNA protection effects of taurine by electron spin resonance spectroscopy. Adv Exp Med Biol, 776:167-177.
11. Froger N, Moutsimilli L, Cadetti L et al (2014). Taurine: the comeback of a neutraceutical in the prevention of retinal degenerations. Prog Retin Eye Res, 41:44-63.
12. Hadj-Saïd W, Fradot V, Ivkovic I et al (2017). Taurine Promotes Retinal Ganglion Cell Survival Through GABAB Receptor Activation. Adv Exp Med Biol, 2:687-701.
13. Zhang X, Lu H, Wang Y et al (2015). Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria. Int J Mol Med, 35(1):218-226.
14. El Agouza IM, Eissa SS, El Houseini MM et al (2011). Taurine: a novel tumor marker for enhanced detection of breast cancer among female patients. Angiogenesis, 14(3):321-330.
15. Yamori Y, Taguchi T, Mori H et al (2010). Low cardiovascular risks in the middle aged males and females excreting greater 24-hour urinary taurine and magnesium in 41 WHO-CARDIAC study populations in the world. J Biomed Sci, 1:S21.
16. Gupta RC, Win T, Bittner S (2005). Taurine analogues; a new class of therapeutics: retrospect and prospects. Curr Med Chem, 12(17):2021-2039.
17. Yuan LQ, Lu Y, Luo XH et al (2007). Taurine promotes connective tissue growth factor (CTGF) expression in osteoblasts through the ERK signal pathway. Amino Acids, 32(3):425-430.
18. Jeon SH, Lee MY, Kim SJ et al (2007). Taurine increases cell proliferation and generates an increase in [Mg2+]i accompanied by ERK 1/2 activation in human osteoblast cells. FEBS Lett, 581(30):5929-5934.
19. Park S, Kim H, Kim SJ (2001). Stimulation of ERK2 by taurine with enhanced alkaline phosphatase activity and collagen synthesis in osteoblast-like UMR-106 cells. Biochem Pharmacol, 62(8):1107-11.
20. Yuan LQ, Liu W, Cui RR et al (2010). Taurine inhibits osteoclastogenesis through the taurine transporter. Amino Acids, 39(1):89-99.
21. Yoo HS, Kim GJ, Song DH et al (2017). Calcium Supplement Derived from Gallus gallus domesticus Promotes BMP-2/RUNX2/SMAD5 and Suppresses TRAP/RANK Expression through MAPK Signaling Activation. Nutrients, 9(5):504.
22. Jeon EJ, Lee DH, Kim YJ et al (2016). Effects of yuja peel extract and its flavanones on osteopenia in ovariectomized rats and osteoblast differentiation. Mol Nutr Food Res, 60(12):2587-2601.
23. Franceschi RT, Xiao G (2003). Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. J Cell Biochem, 88(3):446-454.
24. Ryoo H.M, Lee MH, Kim YJ (2006). Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene, 366(1):51-57.
25. Tural S, Kara N, Alayli G et al (2013). Association between osteoporosis and polymorphisms of the bone Gla protein, estrogen receptor 1, collagen 1-A1 and calcitonin receptor genes in Turkish postmenopausal women. Gene, 515(1):167-172.
26. Prall WC, Haasters F, Heggebö J et al (2013). Mesenchymal stem cells from osteoporotic patients feature impaired signal transduction but sustained osteoinduction in response to BMP-2 stimulation. Biochem Biophys Res Commun, 440(4):617-622.
27. Jang WG, Kim EJ, Kim DK et al (2012). BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription. J Biol Chem, 287(2):905-915.
28. Ge C, Xiao G, Jiang D et al (2007). Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. J Cell Biol, 176(5):709-718.
29. Osyczka AM, Leboy PS (2005). Bone morphogenetic protein regulation of early osteoblast genes in human marrow stromal cells is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. Endocrinology, 146(8):3428-3237.
30. Yoo HS, Chung KH, Lee KJ et al (2017). Melanin extract from Gallus gallus domesticus promotes proliferation and differentiation of osteoblastic MG-63 cells via bone morphogenetic protein-2 signaling. Nutr Res Pract, 11(3):190-197.
31. Someya H, Fujiwara H, Nagata K et al (2015). Thymosin beta 4 is associated with RUNX2 expression through the Smad and Akt signaling pathways in mouse dental epithelial cells. Int J Mol Med, 35(5):1169-1178.
2. Young DR, Niklowitz WJ, Brown RJ et al (1986). Immobilization-associated osteoporosis in primates. Bone, 7(2):109-117.
3. Hollenbach KA, Barrett-Connor E, Edel-stein SL et al (1993). Cigarette Smoking and Bone Mineral Density in Older Men and Women. Am J Public Health, 83(9):1265-1270.
4. Maurel DB, Boisseau N, Benhamou CL et al (2012). Alcohol and bone, review of dose effects and mechanisms. Osteoporos Int, 23(1):1-16.
5. Jang HD, Hong JY, Han K et al (2017). Relationship between bone mineral density and alcohol intake: A nationwide health survey analysis of postmenopausal women. PLoS One, 29;12(6):e0180132.
6. Shams-White MM, Chung M, Du M et al (2017). Dietary protein and bone health, a systematic review and meta-analysis from the National Osteoporosis Foundation. Am J Clin Nutr, 105(6):1528-1543.
7. Huxtable RJ (1992). Physiological Actions of Taurine. Physiol Rev, 72(1):101-63.
8. Yuan LQ, Xie H, Luo XH et al (2006). Taurine transporter is expressed in osteoblasts. Amino Acids, 31(2):157-163.
9. Murakami S (2015). Role of taurine in the pathogenesis of obesity. Mol Nutr Food Res, 59(7):1353-1363.
10. Cheong SH, Moon SH, Lee SJ et al (2013). Antioxidant and DNA protection effects of taurine by electron spin resonance spectroscopy. Adv Exp Med Biol, 776:167-177.
11. Froger N, Moutsimilli L, Cadetti L et al (2014). Taurine: the comeback of a neutraceutical in the prevention of retinal degenerations. Prog Retin Eye Res, 41:44-63.
12. Hadj-Saïd W, Fradot V, Ivkovic I et al (2017). Taurine Promotes Retinal Ganglion Cell Survival Through GABAB Receptor Activation. Adv Exp Med Biol, 2:687-701.
13. Zhang X, Lu H, Wang Y et al (2015). Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria. Int J Mol Med, 35(1):218-226.
14. El Agouza IM, Eissa SS, El Houseini MM et al (2011). Taurine: a novel tumor marker for enhanced detection of breast cancer among female patients. Angiogenesis, 14(3):321-330.
15. Yamori Y, Taguchi T, Mori H et al (2010). Low cardiovascular risks in the middle aged males and females excreting greater 24-hour urinary taurine and magnesium in 41 WHO-CARDIAC study populations in the world. J Biomed Sci, 1:S21.
16. Gupta RC, Win T, Bittner S (2005). Taurine analogues; a new class of therapeutics: retrospect and prospects. Curr Med Chem, 12(17):2021-2039.
17. Yuan LQ, Lu Y, Luo XH et al (2007). Taurine promotes connective tissue growth factor (CTGF) expression in osteoblasts through the ERK signal pathway. Amino Acids, 32(3):425-430.
18. Jeon SH, Lee MY, Kim SJ et al (2007). Taurine increases cell proliferation and generates an increase in [Mg2+]i accompanied by ERK 1/2 activation in human osteoblast cells. FEBS Lett, 581(30):5929-5934.
19. Park S, Kim H, Kim SJ (2001). Stimulation of ERK2 by taurine with enhanced alkaline phosphatase activity and collagen synthesis in osteoblast-like UMR-106 cells. Biochem Pharmacol, 62(8):1107-11.
20. Yuan LQ, Liu W, Cui RR et al (2010). Taurine inhibits osteoclastogenesis through the taurine transporter. Amino Acids, 39(1):89-99.
21. Yoo HS, Kim GJ, Song DH et al (2017). Calcium Supplement Derived from Gallus gallus domesticus Promotes BMP-2/RUNX2/SMAD5 and Suppresses TRAP/RANK Expression through MAPK Signaling Activation. Nutrients, 9(5):504.
22. Jeon EJ, Lee DH, Kim YJ et al (2016). Effects of yuja peel extract and its flavanones on osteopenia in ovariectomized rats and osteoblast differentiation. Mol Nutr Food Res, 60(12):2587-2601.
23. Franceschi RT, Xiao G (2003). Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. J Cell Biochem, 88(3):446-454.
24. Ryoo H.M, Lee MH, Kim YJ (2006). Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene, 366(1):51-57.
25. Tural S, Kara N, Alayli G et al (2013). Association between osteoporosis and polymorphisms of the bone Gla protein, estrogen receptor 1, collagen 1-A1 and calcitonin receptor genes in Turkish postmenopausal women. Gene, 515(1):167-172.
26. Prall WC, Haasters F, Heggebö J et al (2013). Mesenchymal stem cells from osteoporotic patients feature impaired signal transduction but sustained osteoinduction in response to BMP-2 stimulation. Biochem Biophys Res Commun, 440(4):617-622.
27. Jang WG, Kim EJ, Kim DK et al (2012). BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription. J Biol Chem, 287(2):905-915.
28. Ge C, Xiao G, Jiang D et al (2007). Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. J Cell Biol, 176(5):709-718.
29. Osyczka AM, Leboy PS (2005). Bone morphogenetic protein regulation of early osteoblast genes in human marrow stromal cells is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. Endocrinology, 146(8):3428-3237.
30. Yoo HS, Chung KH, Lee KJ et al (2017). Melanin extract from Gallus gallus domesticus promotes proliferation and differentiation of osteoblastic MG-63 cells via bone morphogenetic protein-2 signaling. Nutr Res Pract, 11(3):190-197.
31. Someya H, Fujiwara H, Nagata K et al (2015). Thymosin beta 4 is associated with RUNX2 expression through the Smad and Akt signaling pathways in mouse dental epithelial cells. Int J Mol Med, 35(5):1169-1178.
| Files | ||
| Issue | Vol 48 No 11 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v48i11.3514 | |
| Keywords | ||
| Taurine Osteoporosis Osteoblast ; Ovariectomized rat | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
PARK M, CHOI HK, AN JH. Taurine Activates BMP-2/Wnt3a-Mediated Osteoblast Differentiation and Mineralization via Akt and MAPK Signaling. Iran J Public Health. 2019;48(11):1960-1970.
