Abstract
RANKL induces the formation of osteoclasts, which are responsible for bone resorption. Herein, we investigated the role of SWAP-70-like adapter of T cells (SLAT) in RANKL-induced osteoclastogenesis. Expression levels of SLAT were reduced during RANKL-induced osteoclastogenesis. Overexpression of SLAT in BMMs inhibited TRAP-positive multinuclear osteoclast formation and attenuated the expression of NFATc1, which is an important modulator in osteoclastogenesis. Furthermore, silencing of SLAT by RNA interference enhanced osteoclast formation as well as NFATc1 expression. In addition, SLAT was involved in RANKL-induced JNK activation in osteoclasts. Taken together, our data suggest that SLAT acts as a negative modulator of RANKL-induced osteoclastogenesis.
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Becart, S., Charvet, C., Canonigo Balancio, A.J., De Trez, C., Tanaka, Y., Duan, W., Ware, C., Croft, M., and Altman, A. (2007). SLAT regulates Th1 and Th2 inflammatory responses by controlling Ca2+/NFAT signaling. J. Clin. Invest. 117, 2164–2175.
Boonen, S., and Singer, A.J. (2008). Osteoporosis management: impact of fracture type on cost and quality of life in patients at risk for fracture I. Curr. Med. Res. Opin. 24, 1781–1788.
Borggrefe, T., Wabl, M., Akhmedov, A.T., and Jessberger, R. (1998). A B-cell-specific DNA recombination complex. J. Biol. Chem. 273, 17025–17035.
Boyle, W.J., Simonet, W.S., and Lacey, D.L. (2003). Osteoclast differentiation and activation. Nature 423, 337–342.
Chang, E.J., Ha, J., Huang, H., Kim, H.J., Woo, J.H., Lee, Y., Lee, Z.H., Kim, J.H., and Kim, H.H. (2008). The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation. J. Cell Sci. 121, 2555–2564.
Gupta, S., Fanzo, J.C., Hu, C., Cox, D., Jang, S.Y., Lee, A.E., Greenberg, S., and Pernis, A.B. (2003). T cell receptor engagement leads to the recruitment of IBP, a novel guanine nucleotide exchange factor, to the immunological synapse. J. Biol. Chem. 278, 43541–43549.
Harvey, N., Dennison, E., and Cooper, C. (2010). Osteoporosis: impact on health and economics. Nat. Rev. Rheumatol. 6, 99–105.
Kim, K., Kim, J.H., Lee, J., Jin, H.M., Lee, S.H., Fisher, D.E., Kook, H., Kim, K.K., Choi, Y., and Kim, N. (2005). Nuclear factor of activated T cells c1 induces osteoclast-associated receptor gene expression during tumor necrosis factor-related activationinduced cytokine-mediated osteoclastogenesis. J. Biol. Chem. 280, 35209–35216.
Kim, K., Lee, S.H., Ha Kim, J., Choi, Y., and Kim, N. (2008). NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DCSTAMP). Mol. Endocrinol. 22, 176–185.
Kim, J.H., Kim, K., Jin, H.M., Song, I., Youn, B.U., Lee, J., and Kim, N. (2009). Silibinin inhibits osteoclast differentiation mediated by TNF family members. Mol. Cells 28, 201–207.
Kim, K., Kim, J.H., Moon, J.B., Lee, J., Kwak, H.B., Park, Y.W., and Kim, N. (2012). The transmembrane adaptor protein, linker for activation of T cells (LAT), regulates RANKL-induced osteoclast differentiation. Mol. Cells 33, 401–406.
Lee, Z.H., and Kim, H.H. (2003). Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts. Biochem. Biophys. Res. Commun. 305, 211–214.
Pearce, G., Angeli, V., Randolph, G.J., Junt, T., von Andrian, U., Schnittler, H.J., and Jessberger, R. (2006) Signaling protein SWAP-70 is required for efficient B cell homing to lymphoid organs. Nat. Immunol. 7, 827–834.
Rodan, G.A., and Martin, T.J. (2000). Therapeutic approaches to bone diseases. Science 289, 1508–1514.
Shinohara, M., Terada, Y., Iwamatsu, A., Shinohara, A., Mochizuki, N., Higuchi, M., Gotoh, Y., Ihara, S., Nagata, S., Itoh, H., et al. (2002). SWAP-70 is a guanine-nucleotide-exchange factor that mediates signalling of membrane ruffling. Nature 416, 759–763.
So, H., Rho, J., Jeong, D., Park, R., Fisher, D.E., Ostrowski, M.C., Choi, Y., and Kim, N. (2003). Microphthalmia transcription factor and PU.1 synergistically induce the leukocyte receptor osteoclast-associated receptor gene expression. J. Biol. Chem. 278, 24209–24216.
Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M.T., and Martin, T.J. (1999). Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocrine Rev. 20, 345–357.
Takayanagi, H. (2007). Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat. Rev. 7, 292–304.
Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J., et al. (2002). Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev. Cell 3, 889–901.
Tanaka, Y., Bi, K., Kitamura, R., Hong, S., Altman, Y., Matsumoto, A., Tabata, H., Lebedeva, S., Bushway, P.J., and Altman, A. (2003). SWAP-70-like adapter of T cells, an adapter protein that regulates early TCR-initiated signaling in Th2 lineage cells. Immunity 18, 403–414.
Teitelbaum, S.L. (2000). Bone resorption by osteoclasts. Science 289, 1504–1508.
Walsh, M.C., Kim, N., Kadono, Y., Rho, J., Lee, S.Y., Lorenzo, J., and Choi, Y. (2006). Osteoimmunology: interplay between the immune system and bone metabolism. Ann. Rev. Immunol. 24, 33–63.
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Youn, B.U., Kim, K., Kim, J.H. et al. SLAT negatively regulates RANKL-induced osteoclast differentiation. Mol Cells 36, 252–257 (2013). https://doi.org/10.1007/s10059-013-0159-x
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DOI: https://doi.org/10.1007/s10059-013-0159-x