Long noncoding RNA PVT1 promotes chondrocyte extracellular matrix degradation by acting as a sponge for miR-140 in IL-1β-stimulated chondrocytes.
Long noncoding RNA PVT1 promotes chondrocyte extracellular matrix degradation by acting as a sponge for miR-140 in IL-1β-stimulated chondrocytes.
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DOI：
10.1186/s13018-022-03114-4
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发表时间：
2022-04-10
影响因子：
2.6
通讯作者：
Huang D
中科院分区：
文献类型：
--
作者：
Yao N;Peng S;Wu H;Liu W;Cai D;Huang D
骨关节炎（OA）是一种常见的退行性关节疾病，软骨细胞外基质（ECM）降解是OA的一个重要病理特征。长链非编码RNA （Long noncoding RNA, lncRNA）是一种新型的基因调控因子，在OA等多种疾病的发病机制中起着重要作用。最近的研究证实，lncRNA浆细胞瘤变异易位1 （PVT1）在OA患者中表达上调；然而，其对ECM降解的影响尚不清楚。选取广东省第二中医医院收治的6例OA患者软骨组织标本。从收集的软骨组织中分离培养软骨细胞。在研究过程中进行了质粒构建、RNA干扰、细胞转染、荧光原位杂交（FISH）和拉下实验。在本研究中，在白细胞介素-1β (IL-1β)刺激的软骨细胞中，PVT1的表达显著增加。此外，抑制PVT1可显著下调IL-1β诱导的ADAM金属肽酶（ADAMTS-5）和基质金属蛋白酶-13 （MMP-13）的表达。进一步研究发现PVT1是一种内源性海绵RNA，直接结合miR-140并抑制miR-140的表达。综上所述，本研究表明PVT1作为miR-140的竞争内源性RNA （ceRNA）促进OA中ADAMTS-5和MMP-13的表达，最终导致ECM降解加重，从而为OA的治疗提供了一种新的有希望的策略。
Osteoarthritis (OA) is a common degenerative joint disease, and chondrocyte extracellular matrix (ECM) degradation is one vital pathological feature of OA. Long noncoding RNA (lncRNA), a new kind of gene regulator, plays an important role in pathogenesis of many diseases like OA. Recent studies have confirmed that lncRNA plasmacytoma variant translocation 1 (PVT1) expression was upregulated in OA patients; however, its effect on ECM degradation remained unknown. Cartilage tissue samples were obtained from 6 OA patients admitted in Guangdong Second Traditional Chinese Medicine Hospital. Chondrocytes were isolated and cultured from the collected cartilage tissue. Plasmid construction, RNA interference, cell transfection, fluorescence in situ hybridization (FISH), and pull-down assay were carried out during the research. In this study, PVT1 expression was significantly increased in chondrocytes stimulated by interleukin-1β (IL-1β). In addition, inhibition of PVT1 significantly downregulated the increased expressions of ADAM metallopeptidase with thrombospondin type 1 motif-5 (ADAMTS-5) and matrix metalloproteinase-13 (MMP-13) induced by IL-1β. Further investigation revealed that PVT1 was an endogenous sponge RNA, which directly bound to miR-140 and inhibited miR-140 expression. To sum up, this study showed that PVT1 promoted expressions of ADAMTS-5 and MMP-13 as a competing endogenous RNA (ceRNA) of miR-140 in OA, which eventually led to aggravation of ECM degradation, thus providing a new and promising strategy for the treatment of OA.
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