Whole-Transcriptome Sequence of Degenerative Meniscus Cells Unveiling Diagnostic Markers and Therapeutic Targets for Osteoarthritis.

Whole-Transcriptome Sequence of Degenerative Meniscus Cells Unveiling Diagnostic Markers and Therapeutic Targets for Osteoarthritis.
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DOI:
10.3389/fgene.2021.754421
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发表时间:
2021
影响因子:
3.7
通讯作者:
Zhang Z
Zhang Z
中科院分区:
生物学3区
文献类型:
--
作者:
Jiang Z;Du X;Wen X;Li H;Zeng A;Sun H;Hu S;He Q;Liao W;Zhang Z

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半月板在关节内环境稳定中起着重要作用。半月板的撕裂或退变可能促进膝关节骨关节炎(OA)的发生发展。因此,为了研究半月板退变过程中转录组的变化,我们通过全转录组序列揭示了OA过程中半月板中信使RNA(mRNA)、microRNA(miRNA)、长链非编码RNA(lncRNA)和环状RNA(circRNA)的变化。在用白细胞介素-1 β(IL-1β)处理的退行性半月板中,总共有375种mRNA、15种miRNA、56种lncRNA和90种circRNA发生显著改变。更重要的是,在IL诱导的半月板退变过程中筛选出由lncRNA LOC 107986251-miR-212- 5 p-SESN 3和hsa_circ_0018069-miR-147 b-3 p-TJP 2调控的高度特异性共表达RNA(ceRNA)网络,揭示了OA过程中半月板退变的潜在治疗靶点。此外,脂质运载蛋白-2(LCN 2)和RAB 27 B被确定为半月板退变的潜在生物标志物,通过重叠三个先前构建的OA半月板数据库。LCN 2和RAB 27 B在骨关节炎性骨关节炎和IL-1β治疗的骨关节炎中均上调,并且与OA的严重程度高度相关。这可以将潜在的新型分子引入临床诊断生物标志物数据库和早期OA治疗的可能治疗靶点。
Meniscus plays an important role in joint homeostasis. Tear or degeneration of meniscus might facilitate the process of knee osteoarthritis (OA). Hence, to investigate the transcriptome change during meniscus degeneration, we reveal the alterations of messenger RNA (mRNA), microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA) in meniscus during OA by whole-transcriptome sequence. A total of 375 mRNAs, 15 miRNAs, 56 lncRNAs, and 90 circRNAs were significantly altered in the degenerative meniscus treated with interleukin-1β (IL-1β). More importantly, highly specific co-expression RNA (ceRNA) networks regulated by lncRNA LOC107986251-miR-212-5p-SESN3 and hsa_circ_0018069-miR-147b-3p-TJP2 were screened out during IL-induced meniscus degeneration, unveiling potential therapeutic targets for meniscus degeneration during the OA process. Furthermore, lipocalin-2 (LCN2) and RAB27B were identified as potential biomarkers in meniscus degeneration by overlapping three previously constructed databases of OA menisci. LCN2 and RAB27B were both upregulated in osteoarthritic menisci and IL-1β-treated menisci and were highly associated with the severity of OA. This could introduce potential novel molecules into the database of clinical diagnostic biomarkers and possible therapeutic targets for early-stage OA treatment.
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