Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan, P.R. China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan, P.R. China.
Cell Cycle. 2020 Nov;19(21):2836-2850. doi: 10.1080/15384101.2020.1827188. Epub 2020 Oct 5.
Long non-coding RNAs (lncRNAs) have been noted to influence the progression of ossification of posterior longitudinal ligament (OPLL). The work aims to probe the effect of lncRNA SNHG1 on osteogenic differentiation of ligament fibroblastic cells (LFCs). Aberrantly expressed lncRNAs in ossified PLL tissues were screened out by microarray analysis. Gain- and loss-of function experiments of SNHG1 were performed to identify its role in osteogenic differentiation of LFCs. The downstream molecules of SNHG1 were explored. Altered expression of miR-320b was introduced in LFCs as well. The interactions among SNHG1, miR-320b and IFNGR1 were identified. Consequently, SNHG1 was found highly expressed in OPLL patients. Silencing of SNHG1 inhibited BMP-2, RUNX2 and OCN expression and the ALP activity and reduced osteogenic differentiation of LFCs. Importantly, SNHG1 could and upregulate IFNGR1 through serving as a sponge for miR-320b. Over-expression of miR-320b inhibited osteogenic differentiation of LFCs and inactivated the JAK/STAT signaling pathway. Further administration of Fedratinib, a JAK2-specific agonist, increased osteogenic differentiation of LFCs. To conclude, the study suggested that SNHG1 could upregulate IFNGR1 by sequestering miR-320b and activate the JAK/STAT signaling. Silencing of SNHG1 could reduce the osteogenic differentiation and mineralization of LFCs. The study may offer new insights into OPLL treatment.
长链非编码 RNA（lncRNA）已被证明会影响后纵韧带骨化（OPLL）的进展。本研究旨在探讨 lncRNA SNHG1 对韧带成纤维细胞（LFC）成骨分化的影响。通过基因芯片分析筛选出骨化 PLL 组织中异常表达的 lncRNA。通过 SNHG1 的 gain- 和 loss-of function 实验，确定其在 LFC 成骨分化中的作用。探讨 SNHG1 的下游分子。同时在 LFC 中引入 miR-320b 的改变表达。鉴定 SNHG1、miR-320b 和 IFNGR1 之间的相互作用。结果发现，SNHG1 在 OPLL 患者中高表达。沉默 SNHG1 抑制 BMP-2、RUNX2 和 OCN 表达以及 ALP 活性，并减少 LFC 的成骨分化。重要的是，SNHG1 可以通过作为 miR-320b 的海绵来上调 IFNGR1。过表达 miR-320b 抑制 LFC 的成骨分化并使 JAK/STAT 信号通路失活。进一步给予 JAK2 特异性激动剂 Fedratinib，增加 LFC 的成骨分化。综上所述，该研究表明，SNHG1 通过与 miR-320b 结合而上调 IFNGR1，并激活 JAK/STAT 信号。沉默 SNHG1 可减少 LFC 的成骨分化和矿化。该研究可能为 OPLL 的治疗提供新的思路。
