Abstract
Several studies have suggested a direct link between taurine and bone homeostasis. However, the mechanisms of taurine on the regulation of bone metabolism have not been elucidated. Using a coculture of osteoblasts and bone marrow cells as a model for the study of osteoclastogenesis, RANKL-stimulated RAW264.7 cells and M-CSF- and RANKL-induced bone marrow macrophages were investigated to elucidate the possible roles of taurine in osteoclastogenesis. Taurine inhibited osteoclastogenesis in the coculture of osteoblasts and bone marrow cells, but did not influence the expression of OPG and RANKL in osteoblasts. The taurine transporter (TAUT) expressed by RAW264.7 and bone marrow macrophages exhibited typical taurine uptake activity. Taurine directly reduced osteoclastogenesis in RANKL-stimulated RAW264.7 cells and M-CSF- and RANKL-induced bone marrow macrophages, while TAUT siRNA relieved this effect. Our study demonstrated that taurine directly inhibited osteoclastogenesis through the taurine transporter. Taken together, these data suggest that taurine plays a direct role in bone homeostasis by inhibiting osteoclastogenesis.
Similar content being viewed by others
References
Aubin JE, Bonnelye E (2000) Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. Osteoporos Int 11:905–913
Cheong SH, Chang KJ (2009) The preventive effect of fermented milk supplement containing tomato (Lycopersion esculentum) and taurine on bone loss in ovariectomized rats. Adv Exp Med Biol 643:333–340
Choi MJ, DiMarco NM (2009) The effects of dietary taurine supplementation on bone mineral density in ovariectomized rats. Adv Exp Med Biol 643:341–349
D’Eufemia P, Finocchiaro R, Zambrano A, Tetti M, Ferrucci V, Celli M (2007) Reduction of plasma taurine level in children affected by osteogenesis imperfecta during bisphosphonate therapy. Biomed Pharmacother 61:235–240
Dolder S, Hofstetter W, Wetterwald A, Muhlbauer RC, Felix R (2006) Effect of monoterpenes on the formation and activation of osteoclasts in vitro. J Bone Miner Res 21:647–655
Gupta RC, Kim SJ (2003) Taurine, analogues and bone: a growing relationship. Adv Exp Med Biol 526:323–328
Gupta RC, Win T, Bitter S (2005) Taurine analogues, a new class of therapeutics: retrospect and prospect. Curr Med Chem 1247:2021–2039
Heller-Stilb B, van Roeyen C, Rascher K, Hartwig HG, Huth A, Seeliger MW, Warskulat U, Haussinger D (2002) Disruption of the taurine transporter gene (taut) leads to retinal degeneration in mice. FASEB J 16:231–233
Hofbauer LC, Heufelder AE (2001) Role of receptor activator of nuclear factor-kappa B ligand and osteoprotegerin in bone cell biology. J Mol Med 79:243–253
Holloway WR, Collier FM, Aitken CJ, Myers DE, Hodge JM, Malakellis M, Gough TJ, Collier GR, Nicholson GC (2002) Leptin inhibits osteoclast generation. J Bone Miner Res 17:200–209
Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72:101–163
Jhiang SM, Fithian L, Smanik P, McGill J, Tong Q, Mazzaferri EL (1993) Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett 318:139–144
Kang YS, Kim SJ (2008) The change of taurine transport in osteocytes by oxidative stress, hypertonicity and calcium channel blockers. Biomol Therap 16:219–225
Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142:5050–5055
Kim HW, Kim JH, An HS, Park KK, Kim BK, Park T (2003) Myo-inositol restores the inflammation-induced down-regulation of taurine transport by the murine macrophage cell line, RAW 264.7. Life Sci 73:2477–2489
Kim S, Yamazaki M, Zella LA, Shevde NK, Pike JW (2006) Activation of receptor activator of NF-kappaB ligand gene expression by 1, 25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. Mol Cell Biol 26:6469–6486
Koide M, Okahashi N, Tanaka R, Kazuno K, Shibasaki K, Yamazaki Y, Kaneko K, Ueda N, Ohguchi M, Ishihara Y, Noguchi T, Nishihara T (1999) Inhibition of experimental bone resorption and osteoclast formation and survival by 2-aminoethanesulphonic acid. Arch Oral Biol 44:711–719
Kondo T, Kitazawa R, Maeda S, Kitazawa S (2004) 1 alpha, 25 dihydroxyvitamin D3 rapidly regulates the mouse osteoprotegerin gene through dual pathways. J Bone Miner Res 19:1411–1419
Kum KY, Park JH, Yoo YJ, Choi BK, Lee HJ, Lee SJ (2003) The inhibitory effect of alendronate and taurine on osteoclast differentiation mediated by Porphyromonas gingivalis sonicates in vitro. J Endod 29:28–30
Kwak HB, Lee SW, Li YJ, Kim YA, Han SY, Jhon GJ, Kim HH, Lee ZH (2004) Inhibition of osteoclast differentiation and bone resorption by a novel lysophosphatidylcholine derivative, SCOH. Biochem Pharmacol 67:1239–1248
Lambert IH (2004) Regulation of the cellular content of the organic osmolyte taurine in mammalian cells. Neurochem Res 29:27–63
Lee SE, Woo KM, Kim SY, Kim HM, Kwack K, Lee ZH, Kim HH (2002) The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation. Bone 30:71–77
Liao XB, Zhou XM, Li JM, Tan ZP, Liu LM, Zhang W, Tan H, Lu Y, Yuan LQ (2007) Taurine transporter is expressed in vascular smooth muscle cells. Amino Acids 33:639–643
Liu QR, Lopez-Corcuera B, Nelson H, Mandiyan S, Nelson N (1992) Cloning and expression of a cDNA encoding the transporter of taurine and b-alanine in mouse brain. Proc Natl Acad Sci USA 89:12145–12149
Liu YS, Lu Y, Liu W, Xie H, Luo XH, Wu XP, Yuan LQ, Liao EY (2009) Connective tissue growth factor is a downstream mediator for peptin-induced proliferation and differentiation in human osteoblasts. Amino Acids [Epub ahead of print]
Lubec B, Ya-hua Z, Pertti S, Pentti T, Kizmuller E, Lubec G (1997) Distribution and disappearance of the radiolabeled carbon derived from l-arginine and taurine in the mouse. Life Sci 60:2373–2381
Luo XH, Guo LJ, Xie H, Yuan LQ, Wu XP, Zhou HD, Liao EY (2006) Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signaling pathway. J Bone Miner Res 21:1648–1656
Militante JD, Lombardini JB (2003) Taurine stimulation of calcium uptake in the retina: mechanism of action. Adv Exp Med Biol 526:547–554
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63
Parfitt AM (1987) Bone remodeling and bone loss: understanding the pathophysiology of osteoporosis. Clin Obstet Gynecol 30:789–811
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 62:1107–1111
Pasantes-Morales H, Quesada O, Moran J (1998) Taurine: an osmolyte in mammalian tissues. Adv Exp Med Biol 442:209–217
Ramamoorthy S, Leibach FH, Mahesh VB, Han H, Yang-Feng T, Blakely RD, Ganapathy V (1994) Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem J 300:893–900
Rodan GA (1992) Introduction to bone biology. Bone 13:S3–S6
Rucci N, Rufo A, Alamanou M, Teti A (2007) Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio. J Cell Biochem 100:464–473
Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345–357
Takahashi N, Udagawa N, Suda T (1999) A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function. Biochem Biophys Res Commun 256:449–455
Terauchi A, Nakazaw A, Johkura K, Yan L, Usuda N (1998) Immunohistochemical localization of taurine in various tissue of the mouse. Amino Acids 15:151–160
Uchida S, Kwon HM, Yamauchi A, Preson AS, Marumo F, Handler JS (1992) Molecular cloning of the cDNA for an MDCK cell Nat and Cl-dependent taurine transporter that is regulated by hypertonicity. Proc Natl Acad Sci USA 89:8230–8234
Warskulat U, Flogel U, Jacoby C, Hartwig HG, Thewissen M, Merx MW, Molojavyi A, Heller-Stilb B, Schrader J, Haussinger D (2004) Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised. FASEB J 18:577–579
Wright CE, Tallan HH, Lin YY, Gaull GE (1986) Taurine: biological update. Annu Rev Biochem 55:427–453
Xiao XH, Liao EY, Zhou HD, Dai RC, Yuan LQ, Wu XP (2005) Ascorbic acid inhibits osteoclastogenesis of RAW264.7 cells induced by receptor-activated nuclear factor kappaB ligand (RANKL) in vitro. J Endocrinol Invest 28:253–260
Yasutomi C, Nakamuta H, Fujita T, Takenaga T, Koida M (2002) Anti-osteopenic effect of taurine: possible involvement of activated MEK-ERK-Cbfa1 signaling. Nippon Yakurigaku Zasshi 120:114–115
Yuan LQ, Xie H, Luo XH, Wu XP, Zhou HD, Lu Y, Liao EY (2006) Taurine transporter is expressed in osteoblasts. Amino Acids 31:157–163
Yuan LQ, Lu Y, Luo XH, Xie H, Wu XP, Liao EY (2007) Taurine promotes connective tissue growth factor (CTGF) expression in osteoblasts through the ERK signal pathway. Amino Acids 32:425–430
Zaidi M, Blair HC, Moonga BS, Abe E, Huang CL (2003) Osteoclastogenesis, bone resorption, and osteoclast-based therapeutics. J Bone Miner Res 18:599–609
Acknowledgments
The National Natural Science Foundation of China (No. 30801174) and the Ph. D. Programs Foundation of the Ministry of Education of China (No. 200805331017).
Author information
Authors and Affiliations
Corresponding author
Additional information
L.-Q. Yuan and W. Liu contributed equally to this work.
Rights and permissions
About this article
Cite this article
Yuan, LQ., Liu, W., Cui, RR. et al. Taurine inhibits osteoclastogenesis through the taurine transporter. Amino Acids 39, 89–99 (2010). https://doi.org/10.1007/s00726-009-0380-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-009-0380-2