MicroRNA-34a-5p Promotes Joint Destruction During Osteoarthritis.
MicroRNA-34a-5p Promotes Joint Destruction During Osteoarthritis.
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DOI：
10.1002/art.41552
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Kapoor M
中科院分区：
文献类型：
--
作者：
Endisha H;Datta P;Sharma A;Nakamura S;Rossomacha E;Younan C;Ali SA;Tavallaee G;Lively S;Potla P;Shestopaloff K;Rockel JS;Krawetz R;Mahomed NN;Jurisica I;Gandhi R;Kapoor M
MicroRNA-34 a-5 p（miR-34 a-5 p）在晚期膝关节骨关节炎（OA）患者的滑液中表达升高;然而，其在OA中的确切作用和治疗潜力仍有待充分阐明。本研究旨在研究miR-34 a-5 p在OA发病机制中的作用。在关节组织和人血浆中测定miR-34 a-5 p的表达（n = 71）。在人OA软骨细胞、成纤维细胞样滑膜细胞（FLS）（n = 7-9）和小鼠OA模型（包括内侧半月板不稳定（DMM; n = 22）和喂食高脂饮食并接受DMM的小鼠加速、更严重模型（n = 11））中进行了使用miR-34 a-5 p模拟物或反义寡核苷酸（阿索）处理的实验。对野生型（WT）小鼠（n = 9）和miR-34 a敲除（KO）小鼠（n = 11）进行DMM。结果表示为平均值± SEM，并通过t检验或方差分析以及适当的事后检验进行分析。P值小于0.05被认为是显著的。对WT和KO小鼠软骨细胞进行RNA测序。在晚期OA患者的血浆、软骨和滑膜以及DMM小鼠的软骨和滑膜中，miR-34 a-5 p的表达显著增加。在患有晚期OA的肥胖患者中，以及在喂食高脂饮食的小鼠的血浆和膝关节中，血浆miR-34 a-5 p表达显著增加。在人OA软骨细胞和FLS中，miR-34 a-5 p模拟物增加了关键的OA病理标志物，而miR-34 a-5 p阿索改善了细胞基因表达。关节内注射miR-34 a-5 p模拟物诱导OA样表型。相反，miR-34 a-5 p阿索注射在DMM和高脂饮食/DMM模型中赋予软骨保护作用。miR-34 a-KO小鼠表现出对DMM诱导的软骨损伤的保护作用。WT和KO软骨细胞的RNA测序揭示了推定的miR-34 a-5 p信号传导网络。我们的研究结果为miR-34 a-5 p在OA中的作用和治疗潜力提供了全面的证据。
MicroRNA‐34a‐5p (miR‐34a‐5p) expression is elevated in the synovial fluid of patients with late‐stage knee osteoarthritis (OA); however, its exact role and therapeutic potential in OA remain to be fully elucidated. This study was undertaken to examine the role of miR‐34a‐5p in OA pathogenesis. Expression of miR‐34a‐5p was determined in joint tissues and human plasma (n = 71). Experiments using miR‐34a‐5p mimic or antisense oligonucleotide (ASO) treatment were performed in human OA chondrocytes, fibroblast‐like synoviocytes (FLS) (n = 7–9), and mouse OA models, including destabilization of the medial meniscus (DMM; n = 22) and the accelerated, more severe model of mice fed a high‐fat diet and subjected to DMM (n = 11). Wild‐type (WT) mice (n = 9) and miR‐34a–knockout (KO) mice (n = 11) were subjected to DMM. Results were expressed as the mean ± SEM and analyzed by t‐test or analysis of variance, with appropriate post hoc tests. P values less than 0.05 were considered significant. RNA sequencing was performed on WT and KO mouse chondrocytes. Expression of miR‐34a‐5p was significantly increased in the plasma, cartilage, and synovium of patients with late‐stage OA and in the cartilage and synovium of mice subjected to DMM. Plasma miR‐34a‐5p expression was significantly increased in obese patients with late‐stage OA, and in the plasma and knee joints of mice fed a high‐fat diet. In human OA chondrocytes and FLS, miR‐34a‐5p mimic increased key OA pathology markers, while miR‐34a‐5p ASO improved cellular gene expression. Intraarticular miR‐34a‐5p mimic injection induced an OA‐like phenotype. Conversely, miR‐34a‐5p ASO injection imparted cartilage‐protective effects in the DMM and high‐fat diet/DMM models. The miR‐34a–KO mice exhibited protection against DMM‐induced cartilage damage. RNA sequencing of WT and KO chondrocytes revealed a putative miR‐34a‐5p signaling network. Our findings provide comprehensive evidence of the role and therapeutic potential of miR‐34a‐5p in OA.
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影响因子：
56.9
作者：
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者：
Tuschl, T
影响因子：
2.3
作者：
Díaz-Prado S;Cicione C;Muiños-López E;Hermida-Gómez T;Oreiro N;Fernández-López C;Blanco FJ
通讯作者：
Blanco FJ
影响因子：
13.3
作者：
Remst, D. F. G.;Blom, A. B.;van der Kraan, P. M.
通讯作者：
van der Kraan, P. M.
影响因子：
2.7
作者：
O'Brien, MA;Moravec, RA;Riss, TL
通讯作者：
Riss, TL
影响因子：
4.9
作者：
Murata K;Yoshitomi H;Tanida S;Ishikawa M;Nishitani K;Ito H;Nakamura T
通讯作者：
Nakamura T