溶酶体及其功能障碍影响牙周炎的研究进展

Abstract

Abstract:

Lysosomes are essential organelles for maintaining periodontal tissue homeostasis, and their dysfunction plays a critical role in the initiation and progression of periodontitis. In periodontitis, a persistently acidic microenvironment, continuous pathogenic stimulation, and excessive inflammatory responses can induce multi-level lysosomal dysfunction, including impaired lysosomal acidification, disrupted autophagic flux, and compromised membrane stability. These alterations subsequently affect pathogen clearance, immune regulation, and bone metabolic homeostasis, thereby promoting inflammatory cascade amplification and alveolar bone destruction. This review aims to summarize recent advances in research on the roles of lysosomes and their dysfunction in periodontitis, with the goal of providing new perspectives and a theoretical basis for a deeper understanding of the molecular mechanisms and pharmacological interventions of this disease.

Key words: periodontitis, lysosome, dysfunction

CLC Number:

R781.4

LI Yuanfeng, QIAN Yuanyi, HUANG Yanli, DING Peihui. Research progress of lysosome and its dysfunction in periodontitis[J]. Stomatology, 2026, 46(6): 460-465.

Figures/Tables 1

References 54

[1]	Settembre C, Perera RM. Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology[J]. Nat Rev Mol Cell Biol, 2024, 25(3): 223-245. doi: 10.1038/s41580-023-00676-x
[2]	Retnakumar SV, Geesala R, Bretin A, et al. Targeting the endo-lysosomal autophagy pathway to treat inflammatory bowel diseases[J]. J Autoimmun, 2022, 128: 102814. doi: 10.1016/j.jaut.2022.102814
[3]	Wang AL, Chen C, Mei C, et al. Innate immune sensing of lysosomal dysfunction drives multiple lysosomal storage disorders[J]. Nat Cell Biol, 2024, 26(2): 219-234. doi: 10.1038/s41556-023-01339-x
[4]	Kang S, Liu SX, Dong X, et al. USP4 depletion-driven RAB7A ubiquitylation impairs autophagosome-lysosome fusion and aggravates periodontitis[J]. Autophagy, 2025, 21(4): 771-788. doi: 10.1080/15548627.2024.2429371
[5]	Okano T, Ashida H, Komatsu N, et al. Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A. actinomycetemcomitans exacerbates arthritis[J]. Int J Oral Sci, 2024, 16(1): 54. doi: 10.1038/s41368-024-00315-x
[6]	Ma L, Cao ZG. Periodontopathogen-related cell autophagy-A double-edged sword[J]. Inflammation, 2025, 48(1): 1-14. doi: 10.1007/s10753-024-02049-8
[7]	Shi CS, Shenderov K, Huang NN, et al. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubi-quitinated inflammasomes for destruction[J]. Nat Immunol, 2012, 13(3): 255-263. doi: 10.1038/ni.2215
[8]	苑舒月, 刘春艳, 刘冰, 等. 巨噬细胞的极化与牙周炎[J]. 中国组织工程研究, 2023, 27(17): 2699-2707.
[9]	Liang XF, Liu L, Wang Y, et al. Autophagy-driven NETosis is a double-edged sword-Review[J]. Biomed Pharmacother, 2020, 126: 110065. doi: 10.1016/j.biopha.2020.110065
[10]	Kawai R, Sugisaki R, Miyamoto Y, et al. Cathepsin K degrades osteoprotegerin to promote osteoclastogenesis in vitro[J]. In Vitro Cell Dev Biol Anim, 2023, 59(1): 10-18. doi: 10.1007/s11626-023-00747-5
[11]	Lee SH, Jang JS, Mo SZ, et al. TMEM175 plays a crucial role in osteoblast differentiation by regulating lysosomal function and autophagy[J]. Mol Cells, 2024, 47(11): 100127. doi: 10.1016/j.mocell.2024.100127
[12]	Bonacina F, Zhang XY, Manel N, et al. Lysosomes in the immunometabolic reprogramming of immune cells in atherosclerosis[J]. Nat Rev Cardiol, 2025, 22(3): 149-164. doi: 10.1038/s41569-024-01072-4
[13]	Zhang ZQ, Yue PF, Lu TQ, et al. Role of lysosomes in physiological activities, diseases, and therapy[J]. J Hematol Oncol, 2021, 14(1): 79. doi: 10.1186/s13045-021-01087-1
[14]	Lesbats J, Brillac A, Reisz JA, et al. Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses[J]. Nature, 2025, 640(8058): 524-533. doi: 10.1038/s41586-025-08629-4
[15]	Betancur D, Muñoz Grez C, Oñate A. Comparative analysis of cytokine expression in oral keratinocytes and THP-1 macrophages in response to the most prevalent serotypes of Aggregatibacter actinomycetemcomitans[J]. Microorganisms, 2021, 9(3): 622. doi: 10.3390/microorganisms9030622
[16]	Zhang ZY, Liu DJ, Liu S, et al. The role of Porphyromonas gingivalis outer membrane vesicles in periodontal disease and related systemic diseases[J]. Front Cell Infect Microbiol, 2021, 10: 585917. doi: 10.3389/fcimb.2020.585917
[17]	Park MH, Jeong SY, Na HS, et al. Porphyromonas gingivalis induces autophagy in THP-1-derived macrophages[J]. Mol Oral Microbiol, 2017, 32(1): 48-59. doi: 10.1111/omi.12153 pmid: 26792079
[18]	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. doi: 10.1186/1741-7015-10-122 pmid: 23075094
[19]	Song QY, Meng B, Xu HD, et al. The emerging roles of vacuolar-type ATPase-dependent Lysosomal acidification in neurodegenerative diseases[J]. Transl Neurodegener, 2020, 9(1): 17. doi: 10.1186/s40035-020-00196-0 pmid: 32393395
[20]	Kang S, Dai AN, Wang HM, et al. Interaction between autophagy and Porphyromonas gingivalis-induced inflammation[J]. Front Cell Infect Microbiol, 2022, 12: 892610. doi: 10.3389/fcimb.2022.892610
[21]	de Jongh CA, de Vries TJ, Bikker FJ, et al. Mechanisms of Porphyromonas gingivalis to translocate over the oral mucosa and other tissue barriers[J]. J Oral Microbiol, 2023, 15(1): 2205291. doi: 10.1080/20002297.2023.2205291
[22]	Liu M, Shao J, Zhao Y, et al. Porphyromonas gingivalis evades immune clearance by regulating lysosome efflux[J]. J Dent Res, 2023, 102(5): 555-564. doi: 10.1177/00220345221146097
[23]	Albuquerque-Souza E, Shelling B, Jiang M, et al. Fusobacterium nucleatum triggers senescence phenotype in gingival epithelial cells[J]. Mol Oral Microbiol, 2024, 39(2): 29-39. doi: 10.1111/omi.v39.2
[24]	Ginesin O, Mayer Y, Gabay E, et al. Revealing leukocyte populations in human peri-implantitis and periodontitis using flow cytometry[J]. Clin Oral Investig, 2023, 27(9): 5499-5508. doi: 10.1007/s00784-023-05168-y
[25]	Germic N, Frangez Z, Yousefi S, et al. Regulation of the innate immune system by autophagy: Neutrophils, eosinophils, mast cells, NK cells[J]. Cell Death Differ, 2019, 26(4): 703-714. doi: 10.1038/s41418-019-0295-8 pmid: 30737478
[26]	Watts C. Lysosomes and lysosome-related organelles in immune responses[J]. FEBS Open Bio, 2022, 12(4): 678-693. doi: 10.1002/feb4.v12.4
[27]	Berg RD, Levitte S, O’Sullivan MP, et al. Lysosomal disorders drive susceptibility to tuberculosis by compromising macrophage migration[J]. Cell, 2016, 165(1): 139-152. doi: S0092-8674(16)30136-2 pmid: 27015311
[28]	Pu XP, Qi B. Lysosomal dysfunction by inactivation of V-ATPase drives innate immune response in C. elegans[J]. Cell Rep, 2024, 43(5): 114138. doi: 10.1016/j.celrep.2024.114138
[29]	Figueredo CM, Lira-Junior R, Love RM. T and B cells in periodontal disease: New functions in a complex scenario[J]. Int J Mol Sci, 2019, 20(16): 3949. doi: 10.3390/ijms20163949
[30]	王思健, 王碧瑶, 李嘉慧, 等. 组织蛋白酶在牙周炎进程中作用的研究进展[J]. 中国实用口腔科杂志, 2022, 15(4): 498-503.
[31]	Greabu M, Giampieri F, Imre MM, et al. Autophagy, one of the main steps in periodontitis pathogenesis and evolution[J]. Molecules, 2020, 25(18): 4338. doi: 10.3390/molecules25184338
[32]	Zhang SH, Zhang C, Yan H, et al. Sacral nerve stimulation alleviates intestinal inflammation through regulating the autophagy of macrophages and activating the inflammasome mediated by a cholinergic antiinflammatory pathway in colitis rats[J]. Neuromodulation, 2024, 27(2): 302-311. doi: 10.1016/j.neurom.2023.01.005
[33]	Zhang LJ, Tsai IC, Ni ZH, et al. Copper chelation therapy attenuates periodontitis inflammation through the cuproptosis/autophagy/lysosome axis[J]. Int J Mol Sci, 2024, 25(11): 5890. doi: 10.3390/ijms25115890
[34]	Hornung V, Bauernfeind F, Halle A, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization[J]. Nat Immunol, 2008, 9(8): 847-856. doi: 10.1038/ni.1631 pmid: 18604214
[35]	Jiang WT, Wang YJ, Cao ZL, et al. The role of mitochondrial dysfunction in periodontitis: From mechanisms to therapeutic strategy[J]. J Periodontal Res, 2023, 58(5): 853-863. doi: 10.1111/jre.v58.5
[36]	Lin XJ, Tong XW, Chen YY, et al. The activity, distribution, and colocalization of cathepsin K and matrix metalloproteases in intact and eroded dentin[J]. Clin Oral Investig, 2023, 28(1): 1. doi: 10.1007/s00784-023-05393-5
[37]	Sorsa T, Alassiri S, Grigoriadis A, et al. Active MMP-8 (aMMP-8) as a grading and staging biomarker in the periodontitis classification[J]. Diagnostics, 2020, 10(2): 61. doi: 10.3390/diagnostics10020061
[38]	Yasuda H. Discovery of the RANKL/RANK/OPG system[J]. J Bone Miner Metab, 2021, 39(1): 2-11. doi: 10.1007/s00774-020-01175-1 pmid: 33389131
[39]	Gong Y, Li ZQ, Zou ST, et al. Vangl2 limits chaperone-mediated autophagy to balance osteogenic differentiation in mesenchymal stem cells[J]. Dev Cell, 2021, 56(14): 2103-2120.e9. doi: 10.1016/j.devcel.2021.06.011 pmid: 34214490
[40]	Sun X, Li KX, Hase M, et al. Suppression of breast cancer-associated bone loss with osteoblast proteomes via Hsp90ab1/moesin-mediated inhibition of TGFβ/FN1/CD44 signaling[J]. Theranostics, 2022, 12(2): 929-943. doi: 10.7150/thno.66148
[41]	Duarte C, Yamada C, Garcia C, et al. Crosstalk between dihydroceramides produced by Porphyromonas gingivalis and host lysosomal cathepsin B in the promotion of osteoclastogenesis[J]. J Cell Mol Med, 2022, 26(10): 2841-2851. doi: 10.1111/jcmm.v26.10
[42]	Qin SN, Davern K, Wilson SG, et al. Lysosome-iron-mitochondria axis in osteoclasts: Iron as a central player[J]. Research, 2025, 8: 0840. doi: 10.34133/research.0840
[43]	Radulovic M, Yang CL, Stenmark H. Lysosomal membrane homeostasis and its importance in physiology and disease[J]. Nat Rev Mol Cell Biol, 2026, 27(1): 71-87. doi: 10.1038/s41580-025-00873-w
[44]	Bussi C, Mangiarotti A, Vanhille-Campos C, et al. Stress granules plug and stabilize damaged endolysosomal membranes[J]. Nature, 2023, 623(7989): 1062-1069. doi: 10.1038/s41586-023-06726-w
[45]	Jaber A, Palmieri L, Bakour R, et al. Lysosomal damage is a therapeutic target in Duchenne muscular dystrophy[J]. Sci Adv, 2025, 11(43): eadv6805.
[46]	Beertsen W, Willenborg M, Everts V, et al. Impaired phagosomal maturation in neutrophils leads to periodontitis in lysosomal-associated membrane protein-2 knockout mice[J]. J Immunol, 2008, 180(1): 475-482. doi: 10.4049/jimmunol.180.1.475 pmid: 18097049
[47]	Yang XR, Holliday LS. V-ATPase and lysosomal energy sensing in periodontitis and medicine-related osteonecrosis of the jaw[J]. Biomolecules, 2025, 15(7): 997. doi: 10.3390/biom15070997
[48]	Zhang Y, Shi JY, Zhu J, et al. Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS[J]. Acta Pharm Sin B, 2024, 14(11): 5026-5036. doi: 10.1016/j.apsb.2024.07.008 pmid: 39664434
[49]	Asngari NJM, Bakar KA, Feroz SR, et al. Interaction mechanism of a cysteine protease inhibitor, odanacatib, with human serum albumin: In vitro and bioinformatics studies[J]. Biophys Chem, 2024, 305: 107140. doi: 10.1016/j.bpc.2023.107140
[50]	Jiang H, Dong ZX, Xia XM, et al. Cathepsins in oral diseases: Mechanisms and therapeutic implications[J]. Front Immunol, 2023, 14: 1203071. doi: 10.3389/fimmu.2023.1203071
[51]	Portes J, Bullón B, Quiles JL, et al. Diabetes mellitus and periodontitis share intracellular disorders as the main meeting point[J]. Cells, 2021, 10(9): 2411. doi: 10.3390/cells10092411
[52]	Duan XN, Tong Q, Fu CX, et al. Lysosome-targeted fluorescent probes: Design mechanism and biological applications[J]. Bioorg Chem, 2023, 140: 106832. doi: 10.1016/j.bioorg.2023.106832
[53]	Yin QY, Yang CL. Exploring lysosomal biology: Current approaches and methods[J]. Biophys Rep, 2024, 10(2): 111-120. doi: 10.52601/bpr.2023.230028
[54]	Liu W, Li YJ, An YY, et al. Yunnan Baiyao might mitigate periodontitis bone destruction by inhibiting autophagy and promoting osteoblast differentiation in vivo, ex vivo and in vitro[J]. J Inflamm Res, 2024, 17: 2271-2284. doi: 10.2147/JIR.S454694

Research progress of lysosome and its dysfunction in periodontitis

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