Role of autophagy in the pathogenesis of periodontitis

doi:10.7518/hxkq.2019.04.016

Abstract

Abstract:

Periodontitis is a chronic inflammatory disease of periodontal tissues initiated by oral biofilm. Cellular autophagy is an effective weapon against bacterial infection. Recent studies have shown that autophagy not only promotes the removal of bacteria and toxins from infected cells, but also helps to suppress the inflammatory response to maintain the homeostasis of intracellular environment, which is closely related to the development of periodontitis. Here, we reviewed the relationship between autophagy and periodontitis from three aspects: the interactions between autophagy and periodontal pathogen infection, the regulation of autophagy and immune inflammatory responses, and the relationship between autophagy and alveolar bone metabolism. We aim to provide ideas for further study on the mechanisms of autophagy and periodontitis, and ultimately contribute to a better prevention and treatment of periodontitis.

Key words: periodontitis, autophagy, immunity, inflammation

CLC Number:

R781.4

Longyi Mo,Xiaoyue Jia,Chengcheng Liu,Xuedong Zhou,Xin Xu. Role of autophagy in the pathogenesis of periodontitis[J]. West China Journal of Stomatology, 2019, 37(4): 422-427.

References 51

[1]	Song ZC, Zhou W, Shu R , et al. Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF-1α pathway[J]. Cell Prolif, 2012,45(3):239-248.
[2]	Song B, Zhou T, Yang W , et al. Programmed cell death in periodontitis: recent advances and future perspectives[J]. Oral Dis, 2017,23(5):609-619.
[3]	Deretic V . Autophagy: an emerging immunological paradigm[J]. J Immunol, 2012,189(1):15-20.
[4]	Levine B, Klionsky DJ . Autophagy wins the 2016 Nobel Prize in physiology or medicine: breakthroughs in baker’s yeast fuel advances in biomedical research[J]. Proc Natl Acad Sci U S A, 2017,114(2):201-205.
[5]	Deretic V, Saitoh T, Akira S . Autophagy in infection, inflammation and immunity[J]. Nat Rev Immunol, 2013,13(10):722-737.
[6]	Levine B, Mizushima N, Virgin HW . Autophagy in immunity and inflammation[J]. Nature, 2011,469(7330):323-335.
[7]	Bélanger M, Rodrigues PH, Dunn WA Jr , et al. Autophagy: a highway for Porphyromonas gingivalis in endothelial cells[J]. Autophagy, 2006,2(3):165-170.
[8]	Takeuchi H, Furuta N, Morisaki I , et al. Exit of intracellular Porphyromonas gingivalis from gingival epithelial cells is mediated by endocytic recycling pathway[J]. Cell Microbiol, 2011,13(5):677-691.
[9]	Cho TJ, Wee SW, Woo VH , et al. Porphyromonas gingivalis-induced autophagy suppresses cell proliferation through G1 arrest in oral cancer cells[J]. Arch Oral Biol, 2014,59(4):370-378.
[10]	Blasi I, Korostoff J, Dhingra A , et al. Variants of Porphyromonas gingivalis lipopolysaccharide alter lipidation of autophagic protein, microtubule-associated protein 1 light chain 3, LC3[J]. Mol Oral Microbiol, 2016,31(6):486-500.
[11]	Yamatake K, Maeda M, Kadowaki T , et al. Role for gingipains in Porphyromonas gingivalis traffic to phagolysosomes and survival in human aortic endothelial cells[J]. Infect Immun, 2007,75(5):2090-2100.
[12]	Li L, Michel R, Cohen J , et al. Intracellular survival and vascular cell-to-cell transmission of Porphyromonas gingivalis[J]. BMC Microbiol, 2008,8(1):26.
[13]	Bullon P, Newman HN, Battino M . Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: a shared pathology via oxidative stress and mitochondrial dysfunction[J]. Periodontol 2000, 2014,64(1):139-153.
[14]	Bullon P, Cordero MD, Quiles JL , et al. Autophagy in periodontitis patients and gingival fibroblasts: unraveling the link between chronic diseases and inflammation[J]. BMC Med, 2012,10:122.
[15]	Tsuda H, Ochiai K, Suzuki N , et al. Butyrate, a bacterial metabolite, induces apoptosis and autophagic cell death in gingival epithelial cells[J]. J Periodont Res, 2010,45(5):626-634.
[16]	Levine B, Klionsky DJ . Development by self-digestion: molecular mechanisms and biological functions of autophagy[J]. Dev Cell, 2004,6(4):463-477.
[17]	Álvarez-García Ó, García-López E, Loredo V , et al. Growth hormone improves growth retardation induced by rapamycin without blocking its antiproliferative and antiangiogenic effects on rat growth plate[J]. PLoS One, 2012,7(4):e34788.
[18]	Randow F, Münz C . Autophagy in the regulation of pathogen replication and adaptive immunity[J]. Trends Immunol, 2012,33(10):475-487.
[19]	Hillyer JF . Insect immunology and hematopoiesis[J]. Dev Comp Immunol, 2016,58:102-118.
[20]	El-Awady AR, Miles B, Scisci E , et al. Porphyromonas gingivalis evasion of autophagy and intracellular killing by human myeloid dendritic cells involves DC-SIGN-TLR2 crosstalk[J]. PLoS Pathog, 2015,10(2):e1004647.
[21]	Münz C . Regulation of innate immunity by the molecular machinery of macroautophagy[J]. Cell Microbiol, 2014,16(11):1627-1636.
[22]	Delgado MA, Deretic V . Toll-like receptors in control of immunological autophagy[J]. Cell Death Differ, 2009,16(7):976-983.
[23]	Fang L, Wu HM, Ding PS , et al. TLR2 mediates phagocytosis and autophagy through JNK signaling pathway in Staphylococcus aureus-stimulated RAW264.7 cells[J]. Cell Signal, 2014,26(4):806-814.
[24]	Lee HK, Lund JM, Ramanathan B , et al. Autophagy-dependent viral recognition by plasmacytoid dendritic cells[J]. Science, 2007,315(5817):1398-1401.
[25]	Sumedha S, Kotrashetti V, Nayak R , et al. Immunohistochemical localization of TLR2 and CD14 in gingival tissue of healthy individuals and patients with chronic periodontitis[J]. Biotech Histochem, 2017,92(7):487-497.
[26]	Lin J, Bi LJ, Yu XQ , et al. Porphyromonas gingivalis exacerbates ligature-induced, RANKL-dependent alveolar bone resorption via differential regulation of toll-like receptor 2 (TLR2) and TLR4[J]. Infect Immun, 2014,82(10):4127-4134.
[27]	Morimoto Y, Kawahara KI, Tancharoen S , et al. Tumor necrosis factor-alpha stimulates gingival epithelial cells to release high mobility-group box 1[J]. J Periodontal Res, 2008,43(1):76-83.
[28]	Tang D, Kang R, Livesey KM , et al. Endogenous HMGB1 regulates autophagy[J]. J Cell Biol, 2010,190(5):881-892.
[29]	Zhong ZY, Sanchez-Lopez E, Karin M . Autophagy, inflammation, and immunity: a troika governing cancer and its treatment[J]. Cell, 2016,166(2):288-298.
[30]	Saitoh T, Akira S . Regulation of innate immune responses by autophagy-related proteins[J]. J Cell Biol, 2010,189(6):925-935.
[31]	Kook MS, Park HJ, Oh HK , et al. Trehalose-coated implant for prevention of inflammation in bone[J]. J Oral Maxillofac Surg, 2014,72(9):e28-e29.
[32]	Kim DS, Kim JH, Lee GH , et al. P38 mitogen-activated protein kinase is involved in endoplasmic reticulum stress-induced cell death and autophagy in human gingival fibroblasts[J]. Biol Pharm Bull, 2010,33(4):545-549.
[33]	Oh JE, Lee HK . Pattern recognition receptors and autophagy[J]. Front Immunol, 2014,5:300.
[34]	Nakahira K, Haspel JA, Rathinam VAK , et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome[J]. Nat Immunol, 2011,12(3):222-230.
[35]	Castillo EF, Dekonenko A, Arko-Mensah J , et al. Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation[J]. Proc Natl Acad Sci U S A, 2012,109(46):E3168-E3176.
[36]	Lin NY, Beyer C, Giessl A , et al. Autophagy regulates TNFα-mediated joint destruction in experimental arthritis[J]. Ann Rheum Dis, 2013,72(5):761-768.
[37]	DeSelm CJ, Miller BC, Zou W , et al. Autophagy proteins regulate the secretory component of osteoclastic bone resorption[J]. Dev Cell, 2011,21(5):966-974.
[38]	Lacey DL, Timms E, Tan HL , et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation[J]. Cell, 1998,93(2):165-176.
[39]	Zhao HB, Ito Y, Chappel J , et al. Synaptotagmin Ⅶ regulates bone remodeling by modulating osteoclast and osteoblast secretion[J]. Dev Cell, 2008,14(6):914-925.
[40]	Owen HC, Vanhees I, Gunst J , et al. Critical illness-induced bone loss is related to deficient autophagy and histone hypomethylation[J]. Intensive Care Med Exp, 2015,3(1):52.
[41]	Whitehouse CA, Waters S, Marchbank K , et al. Neighbor of Brca1 gene (Nbr1) functions as a negative regulator of postnatal osteoblastic bone formation and p38 MAPK activity[J]. Proc Natl Acad Sci U S A, 2010,107(29):12913-12918.
[42]	Jia JJ, Yao W, Guan M , et al. Glucocorticoid dose determines osteocyte cell fate[J]. FASEB J, 2011,25(10):3366-3376.
[43]	Zahm AM, Bohensky J, Adams CS , et al. Bone cell autophagy is regulated by environmental factors[J]. Cells Tissues Organs, 2011,194(2/3/4):274-278.
[44]	Xia XC, Kar R, Gluhak-Heinrich J , et al. Glucocorticoid-induced autophagy in osteocytes[J]. J Bone Miner Res, 2010,25(11):2479-2488.
[45]	Onal M, Piemontese M, Xiong JH , et al. Suppression of autophagy in osteocytes mimics skeletal aging[J]. J Biol Chem, 2013,288(24):17432-17440.
[46]	Darcy A, Meltzer M, Miller J , et al. A novel library screen identifies immunosuppressors that promote osteoblast differentiation[J]. Bone, 2012,50(6):1294-1303.
[47]	Pantovic A, Krstic A, Janjetovic K , et al. Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells[J]. Bone, 2013,52(1):524-531.
[48]	Nollet M, Santucci-Darmanin S, Breuil V , et al. Autophagy in osteoblasts is involved in mineralization and bone homeostasis[J]. Autophagy, 2014,10(11):1965-1977.
[49]	Lai EH, Hong CY, Kok SH , et al. Simvastatin alleviates the progression of periapical lesions by modulating autophagy and apoptosis in osteoblasts[J]. J Endod, 2012,38(6):757-763.
[50]	Shapiro IM, Layfield R, Lotz M , et al. Boning up on autophagy[J]. Autophagy, 2014,10(1):7-19.
[51]	Caramés B, Kiosses WB, Akasaki Y , et al. Glucosamine activates autophagy in vitro and in vivo[J]. Arthritis Rheum, 2013,65(7):1843-1852.