Guangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), 60 Hengfu Road, Yuexiu District, Guangzhou City, 510095, Guangdong Province, China.
The Fifth Clinical College of Guangzhou University of Chinese Medicine, 60 Hengfu Road, Yuexiu District, Guangzhou City, 510095, Guangdong Province, China.
J Orthop Surg Res. 2022 Apr 10;17(1):218. doi: 10.1186/s13018-022-03114-4.
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.
骨关节炎（OA）是一种常见的退行性关节疾病，软骨细胞细胞外基质（ECM）降解是 OA 的一个重要病理特征。长链非编码 RNA（lncRNA）作为一种新的基因调节剂，在 OA 等许多疾病的发病机制中发挥着重要作用。最近的研究证实，OA 患者中浆细胞瘤变异易位 1（PVT1）的表达上调，但它对 ECM 降解的影响尚不清楚。
从广东第二中医院收治的 6 例 OA 患者中获取软骨组织样本。从收集的软骨组织中分离和培养软骨细胞。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）和下拉实验。
本研究发现，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 金属肽酶与血小板反应蛋白 1 型基序 5（ADAMTS-5）和基质金属蛋白酶-13（MMP-13）的表达增加。进一步研究表明，PVT1 是一种内源性海绵 RNA，可直接与 miR-140 结合并抑制 miR-140 的表达。
综上所述，本研究表明，PVT1 作为 miR-140 的竞争性内源 RNA（ceRNA），在 OA 中促进 ADAMTS-5 和 MMP-13 的表达，最终导致 ECM 降解加重，为 OA 的治疗提供了一种新的有前景的策略。
