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| Effect of gingival stem cells-derived exosomes on interlukin (IL)-6 and tumor necrosis factor (TNF)-α expression in rats with periodontitis |
| JIANG Ke1, XIAO Wei1, WANG Quanbing2, CHEN Hong1,3
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1. School of Stomatology, Bengbu Medical College, Bengbu, Anhui 233030, China;
2. Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, China;
3. Zhejiang Hospital, Hangzhou, Zhejiang 310030, China |
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Abstract Objective To evaluate the effect of gingival stem cells-derived exosomes (GMSC-Exos) treatment on the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rats with periodontitis, so as to provide the evidence for periodontitis treatment. Methods Forty specific pathogen-free (SPF) rats at ages of 8 weeks were randomly divided into 4 groups, including the blank group, periodontitis group, GMSC-Exos group and PBS group. Rats in the periodontitis group, GMSC-Exos group and PBS group were modeled for periodontitis using the ligature method. Rats in the blank group and periodontitis group were given no treatment, while rats in the GMSC-Exos group and PBS group were given 20 μL GMSC-Exos and PBS by injection, respectively. The periodontal index was measured in all rats 4 weeks post-treatment, and the TNF-α and IL-6 levels were measured in rat serum samples using enzyme-linked immunosorbent assay (ELISA). The TNF-α and IL-6 gene expression was quantified using the polymerase chain reaction (PCR) assay in the gingival tissues of the rat left upper maxillary area, and the periodontal tissues in the left upper maxillary areas were sampled for pathological examinations. Periodontal clinical indexes, IL-6 and TNF-α levels were compared in each group. Results The gingival sulcus bleeding index, gingival index, probing depth, and plaque index in the GMSC-Exos group (1.87±0.41, 1.03±0.19, 1.91±0.09 and 1.11±0.17) were higher than those in the blank group (0.96±0.31, 0.83±0.31, 1.09±0.05 and 1.01±0.38), but lower than those in the periodontitis group (2.65±0.50, 1.36±0.22, 2.61±0.07 and 1.51±0.26) and PBS group (2.44±0.50, 1.23±0.20, 2.49±0.10 and 1.39±0.28) (all P<0.05). The serum IL-6 and TNF-α levels in the GMSC-Exos group [(205.97±11.47) and (90.11±8.57) pg/mL] were higher than those in the blank group [(143.10±4.87) and (80.07±5.13) pg/mL], but lower than those in the periodontitis group [(367.33±13.89) and (158.29±13.10) pg/mL] and PBS group [(364.23±13.62) and (140.60±11.73) pg/mL] (all P<0.05). The IL-6 and TNF-α mRNA expression in the rat gingival tissues in the GMSC-Exos group (1.09±0.14 and 1.61±0.29) was higher than that in the blank group (0.99±0.10 and 1.06±0.14), but lower than that in the periodontitis group (1.63±0.09 and 3.63±0.26) and PBS group (1.58±0.11 and 3.79±0.32) (all P<0.05). Pathological examinations showed alleviation of periodontal tissue destruction, inflammatory cell infiltration and alveolar bone resorption, and no obvious root dental root regeneration in the junctional combined epithelium in the GMSC-Exos group relative to the periodontitis group and the PBS group. Conclusion Administration of GMSC-Exos may reduce periodontal inflammation and alveolar bone resorption by inhibiting IL-6 and TNF-α expression in rats with periodontitis.
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Received: 26 July 2023
Revised: 04 October 2023
Published: 22 November 2023
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[1] MOREIRA P R,LIMA P M,SATHLER K O,et al.Interleukin-6 expression and gene polymorphism are associated with severity of periodontal disease in a sample of Brazilian individuals[J]. Clin Exp Immunol,2007,148(1):119-126.
[2] BARNEA T V,SAVA A,GENTIMIR C,et al.Genetic polymorphisms of TNF-α and IL-1 and generalized aggressive periodontitis[J]. Rom J Morphol Embryol,2015,56(2):459-464.
[3] GARALA K,JOSHI P,SHAH M,et al.Formulation and evaluation of periodontal in situ gel[J]. Int J Pharm Investig,2013,3(1):29-41.
[4] PHINNEY D G,PITTENGER M F.Concise review:MSC-derived exosomes for cell-free therapy[J]. Stem Cells,2017,35(4):851-858.
[5] ZHANG Y L,WANG Z G,SHI B H,et al.Effect of gingival mesenchymal stem cell-derived exosomes on inflammatory macrophages in a high-lipid microenvironment[J/OL]. Int Immunopharmacol,2021,94[2023-10-04]. https://doi.org/10.1016/j.intimp.2021.107455.
[6] ZARUBOVA J,HASANI-SADRABADI M M,DASHTIMOGHADAM E,et al.Engineered delivery of dental stem-cell-derived extracellular vesicles for periodontal tissue regeneration[J/OL]. Adv Healthc Mater,2022,11(12)[2023-10-04]. https://doi.org/10.1002/adhm.202102593.
[7] 孙文东,孙慧斌,刘晓璇,等.牙龈间充质干细胞的培养与鉴定[J]. 青岛大学医学院学报,2017,53(2):157-160.
[8] LI D F,FENG Y,TANG H,et al.A simplified and effective method for generation of experimental murine periodontitis model[J/OL]. Front Bioeng Biotechnol,2020,8[2023-10-04]. https://doi.org/10.3389/fbioe.2020.00444.
[9] TONETTI M S,GREENWELL H,KORNMAN K S.Staging and grading of periodontitis:framework and proposal of a new classification and case definition[J]. J Periodontol,2018,89(Suppl. 1):S159-S172.
[10] ZHANG Q Z,SHI S H,LIU Y,et al.Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis[J]. J Immunol,2009,183(12):7787-7798.
[11] KIM D,LEE A E,XU Q,et al.Gingiva-derived mesenchymal stem cells:potential application in tissue engineering and regenerative medicine-a comprehensive review[J/OL]. Front Immunol,2021,12[2023-10-04]. https://doi.org/10.3389/fimmu.2021.667221.
[12] LIU X,WANG Z,SONG W,et al.Systematically transplanted human gingiva-derived mesenchymal stem cells regulate lipid metabolism and inflammation in hyperlipidemic mice with periodontitis[J]. Exp Ther Med,2020,19(1):672-682.
[13] BLANCO-PINTOS T,REGUEIRA-IGLESIAS A,BALSA-CASTRO C,et al.Update on the role of cytokines as oral biomarkers in the diagnosis of periodontitis[J]. Adv Exp Med Biol,2022,1373:283-302.
[14] ASSUMA R,OATES T,COCHRAN D,et al.IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis[J]. J Immunol,1998,160(1):403-409.
[15] CARDOSO E M,REIS C,MANZANARES-CESPEDES M C.Chronic periodontitis,inflammatory cytokines,and interrelationship with other chronic diseases[J]. Postgrad Med,2018,130(1):98-104. |
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