{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:42:55Z","timestamp":1793234575571,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82101016"],"award-info":[{"award-number":["82101016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82360191"],"award-info":[{"award-number":["82360191"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018571","name":"Guangxi Science and Technology Base and Talent Special Project","doi-asserted-by":"crossref","award":["GuikeAD21220008"],"award-info":[{"award-number":["GuikeAD21220008"]}],"id":[{"id":"10.13039\/501100018571","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation","award":["2023GXNSFBA026125"],"award-info":[{"award-number":["2023GXNSFBA026125"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Oral Health"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Periodontitis is a chronic osteolytic inflammatory disease, where anti-inflammatory intervention is critical for restricting periodontal damage and regenerating alveolar bone. Ropinirole, a dopamine D2 receptor agonist, has previously shown therapeutic potential for periodontitis but the underlying mechanism is still unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Human gingival fibroblasts (HGFs) treated with LPS were considered to mimic periodontitis in vitro. The dosage of Ropinirole was selected through the cell viability of HGFs evaluation. The protective effects of Ropinirole on HGFs were evaluated by detecting cell viability, cell apoptosis, and pro-inflammatory factor levels. The molecular docking between NAT10 and Ropinirole was performed. The interaction relationship between NAT10 and KLF6 was verified by ac4C Acetylated RNA Immunoprecipitation followed by qPCR (acRIP-qPCR) and dual-luciferase reporter assay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Ropinirole alleviates LPS-induced damage of HGFs by promoting cell viability, inhibiting cell apoptosis and the levels of IL-1\u03b2, IL-18, and TNF-\u03b1. Overexpression of NAT10 weakens the effects of Ropinirole on protecting HGFs. Meanwhile, NAT10-mediated ac4C RNA acetylation promotes KLF6 mRNA stability. Upregulation of KLF6 reversed the effects of NAT10 inhibition on HGFs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Taken together, Ropinirole protected HGFs through inhibiting the NAT10 ac4C RNA acetylation to decrease the KLF6 mRNA stability from LPS injury. The discovery of this pharmacological and molecular mechanism of Ropinirole further strengthens its therapeutic potential for periodontitis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12903-024-04250-5","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T06:02:12Z","timestamp":1714456932000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Ropinirole suppresses LPS-induced periodontal inflammation by inhibiting the NAT10 in an ac4C-dependent manner"],"prefix":"10.1186","volume":"24","author":[{"given":"Haiqing","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lufei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"issue":"1","key":"4250_CR1","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1186\/s13287-019-1500-x","volume":"10","author":"L Wu","year":"2019","unstructured":"Wu L, Luo Z, Liu Y, Jia L, Jiang Y, Du J, Guo L, Bai Y, Liu Y. Aspirin inhibits RANKL-induced osteoclast differentiation in dendritic cells by suppressing NF-kappaB and NFATc1 activation. Stem Cell Res Ther. 2019;10(1):375.","journal-title":"STEM CELL RES THER"},{"issue":"1","key":"4250_CR2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1111\/prd.12484","volume":"92","author":"K Jepsen","year":"2023","unstructured":"Jepsen K, Sculean A, Jepsen S. Complications and treatment errors involving periodontal tissues related to orthodontic therapy. Periodontol 2000. 2023;92(1):135\u201358.","journal-title":"PERIODONTOL 2000"},{"issue":"3","key":"4250_CR3","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.identj.2022.01.005","volume":"72","author":"DF Poppolo","year":"2022","unstructured":"Poppolo DF, Ouanounou A. Chlorhexidine in Dentistry: Pharmacology, uses, and adverse effects. Int Dent J. 2022;72(3):269\u201377.","journal-title":"INT DENT J"},{"issue":"1","key":"4250_CR4","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/prd.12331","volume":"84","author":"G Hajishengallis","year":"2020","unstructured":"Hajishengallis G, Chavakis T, Lambris JD. Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy. Periodontol 2000. 2020;84(1):14\u201334.","journal-title":"PERIODONTOL 2000"},{"issue":"1","key":"4250_CR5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41368-022-00177-1","volume":"14","author":"L Xin","year":"2022","unstructured":"Xin L, Zhou F, Zhang C, Zhong W, Xu S, Jing X, Wang D, Wang S, Chen T, Song J. Four-octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system. Int J Oral Sci. 2022;14(1):27.","journal-title":"INT J ORAL SCI"},{"issue":"1","key":"4250_CR6","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s12903-023-03229-y","volume":"23","author":"W Han","year":"2023","unstructured":"Han W, Jiao Y, Mi S, Han S, Xu J, Li S, Liu Y, Guo L. Stevioside reduces inflammation in periodontitis by changing the oral bacterial composition and inhibiting P. Gingivalis in mice. BMC Oral Health. 2023;23(1):550.","journal-title":"BMC Oral Health"},{"key":"4250_CR7","first-page":"D12568","volume":"11","author":"S Khattri","year":"2020","unstructured":"Khattri S, Kumbargere Nagraj S, Arora A, Eachempati P, Kusum CK, Bhat KG, Johnson TM, Lodi G. Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis. Cochrane DB Syst Rev. 2020;11:D12568.","journal-title":"COCHRANE DB SYST REV"},{"issue":"1\u201302","key":"4250_CR8","doi-asserted-by":"publisher","first-page":"39","DOI":"10.18071\/isz.75.0039","volume":"75","author":"OS Gencler","year":"2022","unstructured":"Gencler OS, Oztekin N, Oztekin MF. Comparison of pramipexole versus ropinirole in the treatment of Parkinson\u2019s disease. Ideggyogy Sz. 2022;75(1\u201302):39\u201349.","journal-title":"IDEGGYOGY Sz"},{"key":"4250_CR9","doi-asserted-by":"publisher","first-page":"108216","DOI":"10.1016\/j.neuropharm.2020.108216","volume":"177","author":"F Naz","year":"2020","unstructured":"Naz F, Rahul, Fatima M, Naseem S, Khan W, Mondal AC, Siddique YH. Ropinirole silver nanocomposite attenuates neurodegeneration in the transgenic Drosophila melanogaster model of Parkinson\u2019s disease. Neuropharmacology. 2020;177:108216.","journal-title":"Neuropharmacology"},{"key":"4250_CR10","doi-asserted-by":"crossref","unstructured":"Isozaki Y, Sato T, Takagi R, Ito K, Usui M, Kawano M, Matsushita S. Ropinirole inhibits inflammatory cytokine production in gingival epithelial cells and suppresses alveolar bone loss in an experimental rat model of periodontitis. Exp Ther Med 2023, 25(2).","DOI":"10.3892\/etm.2022.11777"},{"issue":"1","key":"4250_CR11","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s41392-022-00957-5","volume":"7","author":"Y Fan","year":"2022","unstructured":"Fan Y, Cui C, Rosen CJ, Sato T, Xu R, Li P, Wei X, Bi R, Yuan Q, Zhou C. Klotho in Osx(+)-mesenchymal progenitors exerts pro-osteogenic and anti-inflammatory effects during mandibular alveolar bone formation and repair. Signal Transduct Tar. 2022;7(1):155.","journal-title":"SIGNAL TRANSDUCT TAR"},{"issue":"12","key":"4250_CR12","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1161\/CIRCRESAHA.122.322244","volume":"133","author":"J Shi","year":"2023","unstructured":"Shi J, Yang C, Zhang J, Zhao K, Li P, Kong C, Wu X, Sun H, Zheng R, Sun W, et al. NAT10 is involved in Cardiac Remodeling through ac4C-Mediated transcriptomic regulation. CIRC RES. 2023;133(12):989\u20131002.","journal-title":"CIRC RES"},{"issue":"7","key":"4250_CR13","first-page":"119521","volume":"1870","author":"Z Zhang","year":"2023","unstructured":"Zhang Z, Zhang Y, Cai Y, Li D, He J, Feng Z, Xu Q. NAT10 regulates the LPS-induced inflammatory response via the NOX2-ROS-NF-kappaB pathway in macrophages. BBA-MOL CELL RES. 2023;1870(7):119521.","journal-title":"BBA-MOL CELL RES"},{"key":"4250_CR14","doi-asserted-by":"publisher","first-page":"108706","DOI":"10.1016\/j.intimp.2022.108706","volume":"107","author":"X Huang","year":"2022","unstructured":"Huang X, Liu Y, Shen H, Fu T, Guo Y, Qiu S. Chlorogenic acid attenuates inflammation in LPS-induced human gingival fibroblasts via CysLT1R\/Nrf2\/NLRP3 signaling. Int Immunopharmacol. 2022;107:108706.","journal-title":"INT IMMUNOPHARMACOL"},{"issue":"5","key":"4250_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BSR20210138","volume":"41","author":"W Li","year":"2021","unstructured":"Li W, Wang J, Hao W, Yu C. MicroRNA-543-3p down-regulates inflammation and inhibits periodontitis through KLF6. Bioscience Rep. 2021;41(5):1.","journal-title":"BIOSCIENCE REP"},{"key":"4250_CR16","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.neulet.2014.02.053","volume":"566","author":"R Tomasiuk","year":"2014","unstructured":"Tomasiuk R, Szlufik S, Friedman A, Koziorowski D. Ropinirole treatment in Parkinson\u2019s disease associated with higher serum level of inflammatory biomarker NT-proCNP. Neurosci Lett. 2014;566:147\u201350.","journal-title":"NEUROSCI LETT"},{"issue":"10","key":"4250_CR17","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1158\/0008-5472.CAN-22-2233","volume":"83","author":"R Xie","year":"2023","unstructured":"Xie R, Cheng L, Huang M, Huang L, Chen Z, Zhang Q, Li H, Lu J, Wang H, Zhou Q, et al. NAT10 drives cisplatin chemoresistance by enhancing ac4C-Associated DNA repair in bladder Cancer. Cancer Res. 2023;83(10):1666\u201383.","journal-title":"CANCER RES"},{"issue":"5","key":"4250_CR18","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41422-023-00793-4","volume":"33","author":"L Liao","year":"2023","unstructured":"Liao L, He Y, Li SJ, Yu XM, Liu ZC, Liang YY, Yang H, Yang J, Zhang GG, Deng CM, et al. Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner. Cell Res. 2023;33(5):355\u201371.","journal-title":"CELL RES"},{"issue":"2","key":"4250_CR19","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1111\/bju.12603","volume":"114","author":"CL Parsons","year":"2014","unstructured":"Parsons CL, Shaw T, Berecz Z, Su Y, Zupkas P, Argade S. Role of urinary cations in the aetiology of bladder symptoms and interstitial cystitis. BJU Int. 2014;114(2):286\u201393.","journal-title":"BJU INT"},{"key":"4250_CR20","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.cca.2017.02.018","volume":"468","author":"KP Law","year":"2017","unstructured":"Law KP, Han T, Mao X, Zhang H. Tryptophan and purine metabolites are consistently upregulated in the urinary metabolome of patients diagnosed with gestational diabetes mellitus throughout pregnancy: a longitudinal metabolomics study of Chinese pregnant women part 2. Clin Chim Acta. 2017;468:126\u201339.","journal-title":"CLIN CHIM ACTA"},{"issue":"5","key":"4250_CR21","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/j.jpba.2010.07.031","volume":"53","author":"E Szyma\u0144ska","year":"2010","unstructured":"Szyma\u0144ska E, Markuszewski MJ, Markuszewski M, Kaliszan R. Altered levels of nucleoside metabolite profiles in urogenital tract cancer measured by capillary electrophoresis. J Pharmaceut Biomed. 2010;53(5):1305\u201312.","journal-title":"J PHARMACEUT BIOMED"},{"issue":"5","key":"4250_CR22","first-page":"2557","volume":"46","author":"E Borek","year":"1986","unstructured":"Borek E, Sharma OK, Buschman FL, Cohn DL, Penley KA, Judson FN, Dobozin BS, Horsburgh CJ, Kirkpatrick CH. Altered excretion of modified nucleosides and beta-aminoisobutyric acid in subjects with acquired immunodeficiency syndrome or at risk for acquired immunodeficiency syndrome. Cancer Res. 1986;46(5):2557\u201361.","journal-title":"CANCER RES"},{"issue":"1","key":"4250_CR23","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1038\/s42003-022-03868-x","volume":"5","author":"H Zhang","year":"2022","unstructured":"Zhang H, Chen Z, Zhou J, Gu J, Wu H, Jiang Y, Gao S, Liao Y, Shen R, Miao C, et al. NAT10 regulates neutrophil pyroptosis in sepsis via acetylating ULK1 RNA and activating STING pathway. Commun Biol. 2022;5(1):916.","journal-title":"COMMUN BIOL"},{"issue":"4","key":"4250_CR24","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1007\/s10266-023-00793-1","volume":"111","author":"Z Cui","year":"2023","unstructured":"Cui Z, Xu Y, Wu P, Lu Y, Tao Y, Zhou C, Cui R, Li J, Han R. NAT10 promotes osteogenic differentiation of periodontal ligament stem cells by regulating VEGFA-mediated PI3K\/AKT signaling pathway through ac4C modification. Odontology. 2023;111(4):870\u201382.","journal-title":"ODONTOLOGY"},{"key":"4250_CR25","doi-asserted-by":"publisher","first-page":"661731","DOI":"10.3389\/fcell.2021.661731","volume":"9","author":"K Hu","year":"2021","unstructured":"Hu K, Zheng QK, Ma RJ, Ma C, Sun ZG, Zhang N. Kruppel-like factor 6 splice variant 1: an Oncogenic Transcription Factor Involved in the progression of multiple malignant tumors. Front Cell Dev Biol. 2021;9:661731.","journal-title":"FRONT CELL DEV BIOL"},{"issue":"10","key":"4250_CR26","doi-asserted-by":"publisher","first-page":"10902","DOI":"10.1096\/fj.201900867RR","volume":"33","author":"GD Kim","year":"2019","unstructured":"Kim GD, Ng HP, Patel N, Mahabeleshwar GH. Kruppel-like factor 6 and miR-223 signaling axis regulates macrophage-mediated inflammation. Faseb J. 2019;33(10):10902\u201315.","journal-title":"FASEB J"},{"issue":"1","key":"4250_CR27","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1080\/0886022X.2020.1793353","volume":"42","author":"D Li","year":"2020","unstructured":"Li D, Liu X, Li C, Zhang Y, Guan C, Huang J, Xu Y. Role of promoting inflammation of Kr\u00fcppel-like factor 6 in acute kidney injury. Ren Fail. 2020;42(1):693\u2013703.","journal-title":"Ren Fail"},{"key":"4250_CR28","doi-asserted-by":"publisher","first-page":"510","DOI":"10.3389\/fphys.2020.00510","volume":"11","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Li C, Guan C, Zhou B, Wang L, Yang C, Zhen L, Dai J, Zhao L, Jiang W, et al. MiR-181d-5p targets KLF6 to Improve Ischemia\/Reperfusion-Induced AKI through effects on renal function, apoptosis, and inflammation. Front Physiol. 2020;11:510.","journal-title":"FRONT PHYSIOL"}],"container-title":["BMC Oral Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-024-04250-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12903-024-04250-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-024-04250-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T06:02:22Z","timestamp":1714456942000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcoralhealth.biomedcentral.com\/articles\/10.1186\/s12903-024-04250-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4250"],"URL":"https:\/\/doi.org\/10.1186\/s12903-024-04250-5","relation":{},"ISSN":["1472-6831"],"issn-type":[{"value":"1472-6831","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,30]]},"assertion":[{"value":"22 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"510"}}