摘要
目的:观察组蛋白去乙酰化酶3(HDAC3)-核转录因E2相关因子2(Nrf2)信号通路对大鼠颞下颌关节(TMJ)骨关节炎(OA)髁突软骨细胞脂肪化的影响。方法:60只6周龄雌性SD大鼠随机分为10组(n=6),分别为对照组,单侧前牙反(UAC)刺激组,UAC伴HDAC3抑制剂RGFP966注射组(UAC+RGFP966组)以及UAC伴Nrf2激动剂Bardoxolone注射组(UAC+Bardoxolone组),分别于实验开始后4、8、12周处死动物,取TMJ髁突软骨进行HDAC3、Nrf2和软骨细胞脂肪化标志分子脂联素(Adiponectin)免疫组织化学染色。结果:相比于同期对照组,UAC组大鼠TMJ髁突软骨退变明显,HDAC3、Adiponectin阳性细胞率均显著增加(P<0.05),而Nrf2阳性细胞率显著减少(P<0.05);与同期UAC组相比,注射RGFP966和Bardoxolone药物后,大鼠TMJ髁突软骨中HDAC3、Adiponectin阳性细胞率显著减少(P<0.05),Nrf2阳性细胞率显著增多(P<0.05),软骨退变程度显著减轻。结论:UAC刺激通过HDAC3-Nrf2信号通路促进TMJ OA髁突软骨细胞脂肪化,局部药物注射干预HDAC3-Nrf2信号可抑制TMJ OA髁突软骨细胞脂肪化及软骨退变。
Objective:To observe the effects of histone deacetylase 3(HDAC3)-nuclear factor-erythroid 2-related factor 2(Nrf2)signaling pathway on the adipogenesis of condylar chondrocytes in rats with temporomandibular joint(TMJ)osteoarthritis(OA).Methods:606-week-old female SD rats were randomly divided into 10 groups(n=6):control,unilateral anterior crossbite(UAC)stimulation,UAC with HDAC3 inhibitor RGFP966 injection(UAC+RGFP966)and UAC with Nrf2 agonist Bardoxolone injection(UAC+Bardoxolone)groups.The animals were sacrificed at 4,8 and 12 weeks after set up of the experiment,and TMJ condylar cartilage was taken for immunohistochemical(IHC)staining of HDAC3,Nrf2 and Adip onection.Results:Compared with the control group,the degeneration of TMJ condylar cartilage in the UAC group was obvious,the positive cell rates of HDAC3 and Adiponectin were increased(P<0.05),while the positive cell rate of Nrf2 decreased(P<0.05).Compared with UAC group,after injection of RGFP966 and Bardoxolone,the positive cell rates of HDAC3 and Adiponectin in TMJ condylar cartilage of rats were decreased(P<0.05),the positive cell rate of Nrf2 increased(P<0.05),and the degree of cartilage degeneration was reduced.Conclusion:UAC promotes the adipogenesis of TMJ OA condylar chondrocytes through HDAC3-Nrf2 signaling pathway.Local drug injection intervention of HDAC3-Nrf2 signaling can inhibit the adipogenesis and cartilage degeneration of TMJ OA condylar chondrocytes.
作者
师瑜倩
成娟丽
张勉
SHI Yuqian;CHENG Juanli;ZHANG Mian(College of Life Science,Yan'an University,716000,China;State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi International Joint Research Center for Oral Diseases,Department of Oral Anatomy and Physiology and TMD,The Third Hospital Affiliated of Air Force Military Medical University,Xi'an)
出处
《实用口腔医学杂志》
CAS
CSCD
北大核心
2024年第4期480-487,共8页
Journal of Practical Stomatology
基金
陕西省重点研发计划(编号:2023-YBSF-316,2022SF-441)。
