国际口腔医学杂志 ›› 2019, Vol. 46 ›› Issue (2): 197-202.doi: 10.7518/gjkq.2019024

• 牙周专栏 • 上一篇    下一篇

与牙周炎相关的组织蛋白酶研究进展

聂然,郭天奇,李雪,裴婷婷,秦勤,周延民()   

  1. 吉林大学口腔医院种植中心 长春 130021
  • 收稿日期:2018-06-13 修回日期:2018-12-10 出版日期:2019-03-01 发布日期:2019-03-15
  • 通讯作者: 周延民 E-mail:Zhouym62@163.com
  • 作者简介:聂然,硕士,Email: 632529160@qq.com
  • 基金资助:
    国家自然科学基金(81570983)

Research progress on cathepsins related to periodontitis

Ran Nie,Tianqi Guo,Xue Li,Tingting Pei,Qin Qin,Yanmin. Zhou()   

  1. Dept. of Dental Implantology, Hospital of Stomatology, Jilin University, Changchun 130021, China
  • Received:2018-06-13 Revised:2018-12-10 Online:2019-03-01 Published:2019-03-15
  • Contact: Yanmin. Zhou E-mail:Zhouym62@163.com
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81570983)

摘要:

组织蛋白酶是溶酶体中的蛋白质水解酶,在全身疾病(如肿瘤、骨质疏松症、类风湿性关节炎)中的致病作用是当今的研究热点,有大量研究表明其与牙周炎的发生、发展密切相关。组织蛋白酶对于牙周炎的研究以及临床预防和减轻牙周炎具有重要意义。本文就与牙周炎相关的组织蛋白酶K、B、C、G的结构与功能、致病机制及相关抑制剂进行综述。

关键词: 牙周炎, 组织蛋白酶, 组织蛋白酶抑制剂, 核因子

Abstract:

Cathepsin series, also known as proteolysis enzymes in the lysosome, have received attention for their pathology in systemic diseases such as tumour, osteoporosis and rheumatoid arthritis. Many studies have shown that cathepsins are also closely related to the occurrence and progression of periodontitis. Therefore, research on cathepsins towards clinical precaution and alleviation of periodontitis is of great importance. This article reviews the structures, functions, pathogenesis and relevant inhibitors of cathepsins K, B, C and G which are associated with periodontitis.

Key words: periodontitis, cathepsin, cathepsin inhibitor, nuclear factor

中图分类号: 

  • R781.4 +2
[1] Stoka V, Turk V, Turk B . Lysosomal cathepsins and their regulation in aging and neurodegeneration[J]. Ageing Res Rev, 2016,32:22-37.
doi: 10.1016/j.arr.2016.04.010 pmid: 27125852
[2] Novinec M, Kovacic L, Lenarcic B , et al. Conforma-tional flexibility and allosteric regulation of cathepsin K[J]. Biochem J, 2010,429(2):379-389.
doi: 10.1042/BJ20100337 pmid: 20450492
[3] Mort JS, Beaudry F, Théroux K , et al. Early cathepsin K degradation of type Ⅱ collagen in vitro and in vivo in articular cartilage[J]. Osteoarthritis Cartilage, 2016,24(8):1461-1469.
doi: 10.1016/j.joca.2016.03.016 pmid: 27049030
[4] Duong LT . Therapeutic inhibition of cathepsin K—reducing bone resorption while maintaining bone formation[J]. Bonekey Rep, 2012,1:67.
doi: 10.1038/bonekey.2012.67 pmid: 3727753
[5] Mogi M, Otogoto J . Expression of cathepsin-K in gingival crevicular fluid of patients with periodontitis[J]. Arch Oral Biol, 2007,52(9):894-898.
doi: 10.1016/j.archoralbio.2007.01.006 pmid: 17321485
[6] Li YP, Chen W . Characterization of mouse cathepsin K gene, the gene promoter, and the gene expression[J]. JBMR, 1999,14(4):487-499.
doi: 10.1359/jbmr.1999.14.4.487 pmid: 11393791
[7] Balkan W, Martinez AF, Fernandez I , et al. Identi-fication of NFAT binding sites that mediate stimula-tion of cathepsin K promoter activity by RANK ligand[J]. Gene, 2009,446(2):90-98.
doi: 10.1016/j.gene.2009.06.013
[8] Kamolmatyakul S, Chen W, Yang S , et al. IL-1α stimulates cathepsin K expression in osteoclasts via the tyrosine kinase-NF-κB pathway[J]. J Dent Res, 2004,83(10):791-796.
doi: 10.1177/154405910408301011 pmid: 3966556
[9] Knapik DM, Perera P, Nam J , et al. Mechanosignaling in bone health, trauma and inflammation[J]. Antioxid Redox Signal, 2014,20(6):970-985.
doi: 10.1089/ars.2013.5467 pmid: 3924811
[10] Romas E, Gillespie MT, Martin TJ . Involvement of receptor activator of NFκB ligand and tumor necrosis factor-α in bone destruction in rheumatoid arthritis[J]. Bone, 2002,30(2):340-346.
doi: 10.1016/S8756-3282(01)00682-2
[11] Hao L, Chen J, Zhu Z , et al. Odanacatib, a cathepsin K-specific inhibitor, inhibits inflammation and bone loss caused by periodontal diseases[J]. J Periodontol, 2015,86(8):972-983.
doi: 10.1902/jop.2015.140643 pmid: 4648620
[12] Hao L, Zhu G, Lu Y , et al. Deficiency of cathepsin K prevents inflammation and bone erosion in rheuma-toid arthritis and periodontitis and reveals its shared osteoimmune role[J]. FEBS Lett, 2015,589(12):1331-1339.
doi: 10.1016/j.febslet.2015.04.008 pmid: 4623593
[13] Chen W, Gao B, Hao L , et al. The silencing of cathe-psin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation[J]. J Periodontal Res, 2016,51(5):647-660.
doi: 10.1111/jre.12345 pmid: 26754272
[14] Fong D, Chan MM, Hsieh WT , et al. Confirmation of the human cathepsin B gene (CTSB) assignment to chromosome 8[J]. Hum Genet, 1992,89(1):10-12.
doi: 10.1007/BF00207033 pmid: 1577456
[15] Illy C, Quraishi O, Wang J , et al. Role of the occlu-ding loop in cathepsin B activity[J]. J Biol Chem, 1997,272(2):1197-1202.
doi: 10.1074/jbc.272.2.1197 pmid: 8995421
[16] Musil D, Zucic D, Turk D , et al. The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity[J]. EMBO J, 1991,10(9):2321-2330.
doi: 10.1002/embj.1991.10.issue-9
[17] Gondi CS, Rao JS . Cathepsin B as a cancer target[J]. Expert Opin Ther Targets, 2013,17(3):281-291.
doi: 10.4149/neo_2015_003 pmid: 25563363
[18] Cox SW, Eley BM, Kiili M , et al. Collagen degra-dation by interleukin-1β-stimulated gingival fibro-blasts is accompanied by release and activation of multiple matrix metalloproteinases and cysteine proteinases[J]. Oral Dis, 2006,12(1):34-40.
doi: 10.1111/j.1601-0825.2005.01153.x pmid: 16390466
[19] Li X, Wu Z, Ni J , et al. Cathepsin B regulates collagen expression by fibroblasts via prolonging TLR2/NF-κB activation[J]. Oxid Med Cell Longev, 2016,2016:7894247.
doi: 10.1155/2016/7894247 pmid: 27648120
[20] Kennett CN, Cox SW, Eley BM . Ultrastructural localization of cathepsin B in gingival tissue from chronic periodontitis patients[J]. Histochem J, 1997,29(10):727-734.
doi: 10.1023/A:1026465118281 pmid: 9429076
[21] Holden JA, Attard TJ, Laughton KM , et al. Por-phyromonas gingivalis lipopolysaccharide weakly activates M1 and M2 polarized mouse macrophages but induces inflammatory cytokines[J]. Infect Im-mun, 2014,82(10):4190-4203.
doi: 10.1128/IAI.02325-14 pmid: 25047849
[22] 常晓彤, 辇晓峰, 王振辉 . Toll样受体信号转导途径研究进展[J]. 生理科学进展, 2011,42(5):340-346.
Chang XT, Nian XF, Wang ZH . Progress of research on TLRs-mediated signaling pathway[J]. Prog Physiol Sci, 2011,42(5):340-346.
[23] 李倩, 周学东, 樊亚平 , 等. 慢性牙周炎患者唾液蛋白酶谱分析[J]. 华西口腔医学杂志, 2017,35(1):37-42.
doi: 10.7518/hxkq.2017.01.005
Li Q, Zhou XD, Fan YP . Analysis of salivary pro-tease spectrum in chronic periodontitis[J]. West Chin J Stomatol, 2017,35(1):37-42.
doi: 10.7518/hxkq.2017.01.005
[24] Hamon Y, Legowska M, Fergelot P , et al. Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome[J]. FEBS J, 2016,283(3):498-509.
doi: 10.1111/febs.13605 pmid: 26607765
[25] Sørensen OE, Clemmensen SN, Dahl SL , et al. Pa-pillon-Lefèvre syndrome patient reveals species-de-pendent requirements for neutrophil defenses[J]. J Clin Invest, 2014,124(10):4539-4548.
doi: 10.1172/JCI76009 pmid: 4191054
[26] 王津津 . 组织蛋白酶C在牙周炎症反应中的功能初探[D]. 西安: 第四军医大学, 2015.
Wang JJ . A pilot study about the effect of cathepsin C on the periodontal inflammation response[D]. Xi’an: Fourth Military Medical University, 2015.
[27] Khan FY, Jan SM, Mushtaq M . Papillon-Lefevre syndrome (PLS) without cathepsin C mutation: a rare early onset partially penetrant variant of PLS[J]. Saudi Dent J, 2014,26(1):25-28.
doi: 10.1016/j.sdentj.2013.12.004 pmid: 24526825
[28] Türkoğlu O, Azarsız E, Emingil G , et al. Are pro-teinase 3 and cathepsin C enzymes related to patho-genesis of periodontitis[J]. Biomed Res Int, 2014,2014:420830.
doi: 10.1155/2014/420830 pmid: 4052470
[29] Kosikowska P, Lesner A . Inhibitors of cathepsin G: a patent review (2005 to present)[J]. Expert Opin Ther Pat, 2013,23(12):1611-1624.
doi: 10.1517/13543776.2013.835397 pmid: 24079661
[30] 孟焕新 . 牙周病学[M]. 北京: 人民卫生出版社, 2013: 97.
Meng HX. Periodontology[M]. Beijing: People’s Health Publishing House, 2013: 97.
[31] Kurtulus Waschulewski I, Gökbuget AY, Christiansen NM , et al. Immunohistochemical analysis of the gingiva with periodontitis of type Ⅰ plasminogen deficiency compared to gingiva with gingivitis and periodontitis and healthy gingiva[J]. Arch Oral Biol, 2016,72:75-86.
doi: 10.1016/j.archoralbio.2016.07.013 pmid: 27552374
[32] Gul SS, Douglas CW, Griffiths GS , et al. A pilot study of active enzyme levels in gingival crevicular fluid of patients with chronic periodontal disease[J]. J Clin Periodontol, 2016,43(8):629-636.
doi: 10.1111/jcpe.12568 pmid: 27106161
[33] Mukherjee K, Chattopadhyay N . Pharmacological inhibition of cathepsin K: a promising novel approach for postmenopausal osteoporosis therapy[J]. Biochem Pharmacol, 2016,117:10-19.
doi: 10.1016/j.bcp.2016.04.010 pmid: 27106079
[34] 黄伟 . 双磷酸盐相关性颌骨坏死的循证治疗与动物实验模型建立[D]. 武汉: 武汉大学, 2013.
Huang W . Evidence-based therapy and animal model establishment of bisphosphate-related jaw necrosis[D]. Wuhan: Wuhan University, 2013.
[35] Tabatabaei-Malazy O, Salari P, Khashayar P , et al. New horizons in treatment of osteoporosis[J]. Daru, 2017,25(1):2.
doi: 10.1186/s40199-017-0167-z pmid: 28173850
[36] Li YY, Fang J, Ao GZ . Cathepsin B and L inhibitors: a patent review (2010-present)[J]. Expert Opin Ther Pat, 2017,27(6):643-656.
doi: 10.1080/13543776.2017.1272572 pmid: 27998201
[37] Kos J, Mitrović A, Mirković B . The current stage of cathepsin B inhibitors as potential anticancer agents[J]. Future Med Chem, 2014,6(11):1355-1371.
doi: 10.4155/fmc.14.73 pmid: 25163003
[38] Guay D, Beaulieu C, Percival MD . Therapeutic utility and medicinal chemistry of cathepsin C inhibitors[J]. Curr Top Med Chem, 2010,10(7):708-716.
doi: 10.2174/156802610791113469 pmid: 20337582
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