抑制 KCNMA1-AS1 通过 miR-1303/cochlin 轴促进 HBMSCs 的成骨分化。

Inhibiting KCNMA1-AS1 promotes osteogenic differentiation of HBMSCs via miR-1303/cochlin axis.

机构信息

Department of Orthopedics, Fujian Provincial Hospital, Fuzhou, China.

Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.

出版信息

J Orthop Surg Res. 2023 Jan 30;18(1):73. doi: 10.1186/s13018-023-03538-6.

DOI:10.1186/s13018-023-03538-6

PMID:36717952

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9885668/

Abstract

OBJECTIVE

Osteoporosis is a progressive systemic skeletal disorder. Multiple profiling studies have contributed to characterizing biomarkers and therapeutic targets for osteoporosis. However, due to the limitation of the platform of miRNA sequencing, only a part of miRNA can be sequenced based on one platform.

MATERIALS AND METHODS

In this study, we performed miRNA sequencing in osteoporosis bone samples based on a novel platform Illumina Hiseq 2500. Bioinformatics analysis was performed to construct osteoporosis-related competing endogenous RNA (ceRNA) networks. Gene interference and osteogenic induction were used to examine the effect of identified ceRNA networks on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs).

RESULTS

miR-1303 was lowly expressed, while cochlin (COCH) and KCNMA1-AS1 were highly expressed in the osteoporosis subjects. COCH knockdown improved the osteogenic differentiation of HBMSCs. Meanwhile, COCH inhibition compensated for the suppression of osteogenic differentiation of HBMSCs by miR-1303 knockdown. Further, KCNMA1-AS1 knockdown promoted osteogenic differentiation of HBMSCs through downregulating COCH by sponging miR-1303.

CONCLUSIONS

Our findings suggest that the KCNMA1-AS1/miR-1303/COCH axis is a promising biomarker and therapeutic target for osteoporosis.

摘要

目的

骨质疏松症是一种进行性系统性骨骼疾病。多项分析研究有助于确定骨质疏松症的生物标志物和治疗靶点。然而，由于 miRNA 测序平台的限制，基于一个平台只能对一部分 miRNA 进行测序。

材料和方法

本研究基于新型 Illumina Hiseq 2500 平台对骨质疏松症骨样本进行 miRNA 测序。采用生物信息学分析构建与骨质疏松症相关的竞争性内源 RNA（ceRNA）网络。通过基因干扰和成骨诱导实验，研究鉴定的 ceRNA 网络对人骨髓间充质干细胞（HBMSCs）成骨分化的影响。

结果

在骨质疏松症患者中，miR-1303 表达下调，而 cochlin（COCH）和 KCNMA1-AS1 表达上调。COCH 敲低可促进 HBMSCs 的成骨分化。同时，COCH 抑制可通过海绵吸附 miR-1303 来补偿 miR-1303 敲低对 HBMSCs 成骨分化的抑制作用。此外，KCNMA1-AS1 敲低通过下调 COCH 促进 HBMSCs 的成骨分化。