Effect of inflammatory exosomes derived from different synoviocytes on rabbit knee joint and its mechanism based on TLRs/NF-κB signal pathway
ZHOU Jun1 GUO Changqing2 WANG Qingfu3
1.Graduate School of Beijing University of Chinese Medicine, Beijing 100029, China;
2.School of Acupuncture and Massage, Beijing University of Chinese Medicine, Beijing 100029, China;
3.Department of Tendon Injury, the Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100029, China
Abstract：Objective To observe the effect of inflammatory exosomes derived from different synoviocytes on rabbit knee joint and its mechanism based on TLRs/NF-κB signal pathway. Methods Two synoviocytes were treated with lipopolysaccharide to induce inflammation, the exosomes were extracted separately. Twenty experimental rabbits were divided into five groups by random number table method: normal group, saline group, group A (injected with exosome suspension of A cell), group B (injected with exosome suspension of B cell), and group A+B (injected with two kinds of exosome mixed suspension), with four rabbits in each group. The normal group was not treated, the saline group was injected with normal saline, and the corresponding exosome suspension was injected into the joint cavity of rabbits in the exosome group (the concentration was 1×107/ml). After two weeks of intervention, the behavioral changes of rabbits in each group were recorded, and the expression levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6 and matrix metalloproteinase 13 (MMP-13) in serum were detected by enzyme-linked immunosorbent assay, Toll-like receptor 2 (TLR2), P65, myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factor 2 (traf2) were detected by Western blot. Results There was no significant difference in behavioral Lequesne MG index between normal group and saline group before and after intervention (P＞0.05). The behavioral Lequesne MG index of rabbits in groups A, B and A+B after intervention was higher than that before intervention, and higher than that in normal group (P＜0.05); the levels of TNF-α, IL-1β, IL-6, and MMP-13 in serum and the expressions of TLR2, P65, MyD88, and traf2 in synovium tissue of rabbits in groups A, B and A+B were higher than those in normal group (P＜0.05); the levels of TNF-α, IL-1β, IL-6, and MMP-13 in serum of rabbits , and the levels of TLR2, P65, MyD88, and traf2 in synovium in group A+B were higher than those in groups A and B (P＜0.05). The protein expressions of TLR2, P65, MyD88, and traf2 in synovium tissue of rabbits in group A were higher than those in group B (P＜0.05). Conclusion Both kinds of synoviocytes secretions in inflammatory environment can activate synovial TLRs/NF-κB signal pathway aggravates synovial inflammation.
周俊1 郭长青2 王庆甫3. 基于TLRs/NF-κB信号通路观察不同滑膜细胞来源炎性外泌体对家兔膝关节的影响及其作用机制[J]. 中国医药导报, 2023, 20(27): 12-15.
ZHOU Jun1 GUO Changqing2 WANG Qingfu3. Effect of inflammatory exosomes derived from different synoviocytes on rabbit knee joint and its mechanism based on TLRs/NF-κB signal pathway. 中国医药导报, 2023, 20(27): 12-15.
[1] Jankaew A，You YL，Yang TH，et al. The effects of low-level laser therapy on muscle strength and functional outcomes in individuals with knee osteoarthritis：a double-blinded randomized controlled trial [J]. Sci Rep，2023，13（1）：165.
[2] Kan HS，Chan PK，Chiu KY，et al. Non-surgical treatment of knee osteoarthritis [J]. Hong Kong Med J，2019，25（2）：127- 133.
[3] Jang S，Lee K，Ju JH. Recent Updates of Diagnosis，Pathophysiology，and Treatment on Osteoarthritis of the Knee [J]. Int J Mol Sci，2021，22（5）：2619.
[4] Primorac D，Molnar V，Rod E，et al. Knee Osteoarthritis：A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations [J]. Genes （Basel），2020，11（8）：854.
[5] Cai W，Li H，Zhang Y，et al. Identification of key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis [J]. Peer J，2020，8：e8390.
[6] 井维尧，杜小正，田杰祥，等.基于TLR4/NF-κB通路的类风湿性关节炎滑膜炎症发病机制及中医药治疗研究进展[J].甘肃中医药大学学报，2022，39（2）：84-89.
[7] 阮安民，王庆甫，马玉峰，等.电针对膝骨关节炎兔NF-κB信号通路及滑膜炎症的影响[J].现代中西医结合杂志，2021，30（28）：3095-3099.
[8] 赵泽明，张柳.NF-κB信号通路与骨关节炎的关系研究进展[J].华北理工大学学报（医学版），2021，23（3）：232- 238.
[9] 毛骁，肖艳，郭洁梅，等.壮骨健膝方对兔膝骨关节炎滑膜炎症肝X受体/核因子κB通路的影响[J].世界中医药，2021，16（21）：3198-3203.
[10] Zhao J，Li X，Hu J，et al. Mesenchymal stromal cell- derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization [J]. Cardiovasc Res，2019，115（7）：1205-1216.
[11] Luo Q，Guo D，Liu G，et al. Exosomes from MiR-126- Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury [J]. Cell Physiol Biochem，2017，44（6）：2105-2116.
[12] Deng S，Zhou X，Ge Z，et al. Exosomes from adipose-derived mesenchymal stem cells ameliorate cardiac damage after myocardial infarction by activating S1P/SK1/S1PR1 signaling and promoting macrophage M2 polarization [J]. Int J Biochem Cell Biol，2019，114：105564.
[13] 吴文哲，付长秀，黄李晨，等.外泌体通过NF-κB信号通路调节骨关节炎的炎症反应[J].中国免疫学杂志，2022，38（22）：2689-2694，2699.
[14] Yang YH，Liu TH，Zhang LD，et al. Role of the PERK-eIF2α-CHOP Signaling Pathway in the Effect of Needle Knife Therapy on Knee Joint Chondrocyte Apoptosis [J]. Evid Based Complement Alternat Med，2019，2019：7164916.
[15] Tu J，Hong W，Zhang P，et al. Ontology and Function of Fibroblast-Like and Macrophage-Like Synoviocytes：How Do They Talk to Each Other and Can They Be Targeted for Rheumatoid Arthritis Therapy [J]. Front Immunol，2018，9：1467.
[16] Feldt J，Schicht M，Welss J，et al. Production and Secretion of Gelsolin by Both Human Macrophage-and Fibroblast-like Synoviocytes and GSN Modulation in the Synovial Fluid of Patients with Various Forms of Arthritis [J]. Biomedicines，2022，10（3）：723.
[17] 韩广弢，李皓桓，张宇标，等.滑膜在炎性关节病中的作用[J].广西医学，2019，41（12）：1545-1548.
[18] 陈鹏，郭洁梅，肖艳，等.基于LXRs/NF-κB信号通路对A型滑膜细胞的调控探讨壮骨健膝方的作用机制[J].中国中西医结合杂志，2022，42（9）：1087-1094.
[19] 任立桐，姚志城，喻晓龙.基于NF-κB信号通路探讨牛膝总皂苷治疗膝骨性关节炎滑膜炎症效果机制[J].中国中医药现代远程教育，2023，21（6）：164-166.
[20] 张栋，王庆甫，张晓哲，等.β-catenin与NF-κB信号通路在膝骨关节炎滑膜炎症中的表达特点及意义[J].中国骨伤，2019，32（8）：721-726.
[21] Miller RE，Scanzello CR，Malfait AM. An emerging role for Toll-like receptors at the neuroimmune interface in osteoarthritis [J]. Semin Immunopathol，2019，41（5）：583-594.
[22] 李娟，周颖，谭钢，等.间充质干细胞外泌体治疗小鼠干眼的疗效评价[J].眼科新进展，2019，39（10）：901-905.
[23] Smith MD，Barg E，Weedon H，et al.Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints [J]. Ann Rheum Dis，2003，62（4）：303-307.
[24] Jakubzick C，Gautier EL，Gibbings SL，et al. Minimal differentiation of classical monocytes as they survey steady- state tissues and transport antigen to lymph nodes [J]. Immunity，2013，39（3）：599-610.
[25] Hoeffel G，Wang Y，Greter M，et al. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages [J]. J Exp Med，2012，209（6）：1167-1181.
京公网安备 11010502046598号