Browse > Article
http://dx.doi.org/10.14348/molcells.2017.0230

Lipopolysaccharide (LPS)-Induced Autophagy Is Responsible for Enhanced Osteoclastogenesis  

Sul, Ok-Joo (Department of Biological Sciences, University of Ulsan)
Park, Hyun-Jung (Department of Biological Sciences, University of Ulsan)
Son, Ho-Jung (Department of Biological Sciences, University of Ulsan)
Choi, Hye-Seon (Department of Biological Sciences, University of Ulsan)
Publication Information
Molecules and Cells / v.40, no.11, 2017 , pp. 880-887 More about this Journal
Abstract
We hypothesized that inflammation affects number and activity of osteoclasts (OCs) via enhancing autophagy. Lipopolysaccharide (LPS) induced autophagy, osteoclastogenesis, and cytoplasmic reactive oxygen species (ROS) in bone marrow-derived macrophages that were pre-stimulated with receptor activator of nuclear $factor-{\kappa}B$ ligand. An autophagy inhibitor, 3-methyladenine (3-MA) decreased LPS-induced OC formation and bone resorption, indicating that autophagy is responsible for increasing number and activity of OCs upon LPS stimulus. Knockdown of autophagy-related protein 7 attenuated the effect of LPS on OC-specific genes, supporting a role of LPS as an autophagy inducer in OC. Removal of ROS decreased LPS-induced OC formation as well as autophagy. However, 3-MA did not affect LPS-induced ROS levels, suggesting that ROS act upstream of phosphatidylinositol-4,5-bisphosphate 3-kinase in LPS-induced autophagy. Our results suggest the possible use of autophagy inhibitors targeting OCs to reduce inflammatory bone loss.
Keywords
autophagy; lipopolysaccharide; osteoclast;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Budanov, A.V., and Karin, M. (2008). p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 134, 451-460.   DOI
2 Cejka, D., Hayer, S., Niederreiter, B., Sieghart, W., Fuereder, T., Zwerina, J., and Schett, G. (2010). Mammalian target of rapamycin signaling is crucial for joint destruction in experimental arthritis and is activated in osteoclasts from patients with rheumatoid arthritis. Arthritis Rheum. 62, 2294-2302.   DOI
3 Chamoux, E., Couture, J., Bisson, M., Morissette, J., Brown, J.P., and Roux, S. (2009). The p62 P392L mutation linked to Paget's disease induces activation of human osteoclasts. Mol. Endocrinol. 23, 1668-1680.   DOI
4 Chang, N.C., Nguyen, M., Germain, M., and Shore, G.C. (2010). Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. EMBO J. 29, 606-618.   DOI
5 Chen, Y., McMillan-Ward, E., Kong, J., Israels, S.J., and Gibson, S.B. (2007). Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. J. Cell Sci. 120, 4155-4166.   DOI
6 Chen, Y., Azad, M.B., and Gibson, S.B. (2009). Superoxide is the major reactive oxygen species regulating autophagy. Cell Death Differ. 16, 1040-1052.   DOI
7 Chung, Y.H., Yoon, S.Y., Choi, B., Sohn, D.H., Yoon, K.H., Kim, W.J., Kim, D.H., and Chang, E.J. (2012). Microtubule-associated protein light chain 3 regulates Cdc42-dependent actin ring formation in osteoclast. Int. J. Biochem. Cell Biol. 44, 989-997.   DOI
8 Dames, S.A., Mulet, J.M., Rathgeb-Szabo, K., Hall, M.N., and Grzesiek, S. (2005). The solution structure of the FATC domain of the protein kinase target of rapamycin suggests a role for redox-dependent structural and cellular stability. J. Biol. Chem. 280, 20558-20564.   DOI
9 Fujita, K., Maeda, D., Xiao, Q., and Srinivasula, S.M. (2011). Nrf2-mediated induction of p62 controls Toll-like receptor-4-driven aggresome-like induced structure formation and autophagic degradation. Proc. Natl. Acad. Sci. USA 108, 1427-1432.   DOI
10 DeSelm, C.J., Miller, B.C., Zou, W., Beatty, W.L., van Meel, E., Takahata, Y., Klumperman, J., Tooze, S.A., Teitelbaum, S.L., and Virgin, H.W. (2011). Autophagy proteins regulate the secretory component of osteoclastic bone resorption. Dev. Cell 21, 966-974.   DOI
11 Huang, J., and Brumell, J.H. (2009). NADPH oxidases contribute to autophagy regulation. Autophagy 5, 887-889.   DOI
12 Jimi, E., Akiyama, S., Tsuruka,i T., Okahashi, N., Kobayashi, K., Udagawa, N., Nishihara, T., and Suda, T. (1999). Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function. J. Immunol. 163, 434-442.
13 Ke, K., Sul, O.J., Choi, E.K., Safdar, A.M., Kim, E.S., and Choi, H.S. (2014). Reactive oxygen species induce the association of SHP-1 with c-Src and the oxidation of both to enhance osteoclast survival. Am. J. Physiol. Endocrinol. Metab. 307, E61-E70   DOI
14 Sato, M., Bryant, H.U., Dodge, J.A., Davis, H., Matter, W.F., and Vlahos, C.J. (1996). Effects of wortmannin analogs on bone in vitro and in vivo. J. Pharmacol. Exp. Ther. 277, 543-550.
15 Kirkland, R.A., Adibhatla, R.M., Hatcher, J.F., and Franklin, J.L. (2002). Loss of cardiolipin and mitochondria during programmed neuronal death: evidence of a role for lipid peroxidation and autophagy. Neuroscience 115, 587-602.   DOI
16 Lee, N.K., Choi, Y.G., Baik, J.Y., Han, S.Y., Jeong, D.W., Bae, Y.S., Kim, N., and Lee, S.Y. (2005). A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood 106, 852-859.   DOI
17 Lin, N.Y., Beyer, C., Giessl, A., Kireva, T., Scholtysek, C., Uderhardt, S., Munoz, L.E., Dees, C., Distler, A., Wirtz, S., et al. (2013). Autophagy regulates $TNF{\alpha}$-mediated joint destruction in experimental arthritis. Ann. Rheum. Dis. 72, 761-768.   DOI
18 Orcel, P., Feuga, M., Bielakoff, J., and De Vernejoul, M.C. (1993). Local bone injections of LPS and M-CSF increase bone resorption by different pathways in vivo in rats. Am. J. Physiol. 264, E391-397.
19 Park, H., Noh, A., Long, S.M., Kang, J., Sim, J., Lee, D., and Yim, M. (2014). Peroxiredoxin II negatively regulates lipopolysaccharide-induced osteoclast formation and bone loss via JNK and STAT3. Antioxid. Redox Signal. 22, 63-77.
20 Scherz-Shouval, R., Shvets, E., Fass, E., Shorer, H., Gil, L., and Elazar, Z. (2007). Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 26, 1749-1760.   DOI
21 Sharifi, M.N., Mowers, E.E., Drake, L.E., and Macleod, K.F. (2015). Measuring autophagy in stressed cells. Methods Mol. Biol. 1292, 129-150.
22 Wang, K., Niu, J., Kim, H., and Kolattukudy, P.E. (2011). Osteoclast precursor differentiation by MCPIP via oxidative stress, endoplasmic reticulum stress, and autophagy. J. Mol. Cell Biol. 3, 360-368.   DOI
23 Shi, J., Wang, L., Zhang, H., Jie, Q., Li, X., Shi, Q., Huang, Q., Gao, B., Han, Y., Guo, K., et al. (2015). Glucocorticoids: dose-related effects on osteoclast formation and function via reactive oxygen species and autophagy. Bone 79, 222-232.   DOI
24 Takami, M., Kim, N., Rho, J., and Choi, Y. (2002). Stimulation by toll-like receptors inhibits osteoclast differentiation. J. Immunol. 169, 1516-1523.   DOI
25 Ti, Y., Zhou, L., Wang, R., and Zhao, J. (2015). Inhibition of microtubule dynamics affects podosome belt formation during osteoclast induction. Cell Biochem. Biophys. 71, 741-747.   DOI
26 Xiu, Y., Xu, H., Zhao, C., Li, J., Morita, Y., Yao, Z., Xin, L., and Boyce, B.F. (2014). Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation. J. Clin. Invest. 124, 297-310.   DOI
27 Zhang, L., Guo, Y.F., Liu, Y.Z., Liu, Y.J., Xiong, D.H., Liu, X.G., Wang, L., Yang, T.L., Lei, S.F., Guo, Y., et al. (2010). Pathway-based genome-wide association analysis identified the importance of regulation-of-autophagy pathway for ultradistal radius BMD. J. Bone Miner. Res. 25, 1572-1580.   DOI
28 Zhong, Y., Wang, Q.J., Li, X., Yan, Y., Backer, J.M., Chait, B.T., Heintz, N., and Yue, Z. (2009). Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat. Cell Biol. 11, 468-476.   DOI
29 Zhao, Y., Chen, G., Zhang, W., Xu, N., Zhu, J.Y., Jia, J., Sun, Z.J., Wang, Y.N., and Zhao, Y.F. (2012). Autophagy regulates hypoxia-induced osteoclastogenesis through the HIF-$1{\alpha}$/BNIP3 signaling pathway. J. Cell. Physiol. 227, 639-648.   DOI