Department of Orthopedic Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
Department of Nursing, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
J Cell Mol Med. 2023 Jan;27(2):189-203. doi: 10.1111/jcmm.17633. Epub 2022 Dec 20.
Circular RNAs (circRNAs) are often found in eukaryocyte and have a role in the pathogenesis of a variety of human disorders. Our related research has shown the differential expression of circRNAs in periprosthetic osteolysis (PPOL). However, the involvement of circRNAs in the exact process is yet unknown. CircSLC8A1 expression was evaluated in clinical samples and human bone marrow mesenchymal stem cells (hBMSCs) in this investigation using quantitative real-time PCR. In vitro and in vivo studies were conducted to explicate its functional role and pathway. We demonstrated CircSLC8A1 is involved in PPOL using gain- and loss-of-function methods. The association of CircSLC8A1 and miR-144-3p, along with miR-144-3p and RUNX1, was predicted using bioinformatics. RNA pull-down and luciferase assays confirmed it. The impact of CircSLC8A1 in the PPOL-mouse model was also investigated using adeno-associated virus. CircSLC8A1 was found to be downregulated in PPOL patients' periprosthetic tissues. Overexpression of CircSLC8A1 promoted osteogenic differentiation (OD) and inhibited apoptosis of hBMSCs in vitro. The osteogenic markers of RUNX1, osteopontin (OPN) and osteocalcin (OCN) were significantly upregulated in hBMSCs after miR-144-3p inhibitor was transferred. Mechanistic analysis demonstrated that CircSLC8A1 directly bound to miR-144-3p and participated in PPOL through the miR-144-3p/RUNX1 pathway in hBMSCs. Micro-CT and quantitative analysis showed that CircSLC8A1 markedly inhibited PPOL, and osteogenic markers (RUNX1, OPN and OCN) were significantly increased (P<0.05) in the mice model. Our findings prove that CircSLC8A1 exerted a regulatory role in promoting osteogenic differentiation in hBMSCs, and CircSLC8A1/miR-144-3p/RUNX1 pathway may provide a potential target for prevention of PPOL.
环状 RNA（circRNAs）通常存在于真核细胞中，在多种人类疾病的发病机制中发挥作用。我们的相关研究表明，环状 RNA 在假体周围骨溶解（PPOL）中存在差异表达。然而，其在确切过程中的参与尚不清楚。在这项研究中，使用定量实时 PCR 评估了临床样本和人骨髓间充质干细胞（hBMSCs）中的 circSLC8A1 表达。通过体外和体内研究来阐明其功能作用和途径。我们使用增益和失活功能方法证明 CircSLC8A1 参与了 PPOL。使用生物信息学预测了 CircSLC8A1 与 miR-144-3p 以及 miR-144-3p 和 RUNX1 的关联。RNA 下拉和荧光素酶测定证实了这一点。还使用腺相关病毒研究了 CircSLC8A1 在 PPOL-小鼠模型中的影响。在 PPOL 患者假体周围组织中发现 CircSLC8A1 下调。CircSLC8A1 的过表达促进了 hBMSCs 的成骨分化（OD）并抑制了其凋亡。转染 miR-144-3p 抑制剂后，hBMSCs 中的成骨标志物 RUNX1、骨桥蛋白（OPN）和骨钙素（OCN）显著上调。机制分析表明，CircSLC8A1 直接与 miR-144-3p 结合，并通过 hBMSCs 中的 miR-144-3p/RUNX1 途径参与 PPOL。Micro-CT 和定量分析表明，CircSLC8A1 显著抑制了 PPOL，并且在小鼠模型中，成骨标志物（RUNX1、OPN 和 OCN）显著增加（P<0.05）。我们的研究结果证明 CircSLC8A1 在促进 hBMSCs 成骨分化中发挥调节作用，CircSLC8A1/miR-144-3p/RUNX1 途径可能为预防 PPOL 提供潜在的靶点。
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