Department of Trauma and Joint, The Second Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066600, China.
Department of Gastroenterology and Nephrology, The Second Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066600, China.
Genes Genomics. 2021 May;43(5):523-531. doi: 10.1007/s13258-021-01038-7. Epub 2021 Mar 16.
Most fractures could heal after treatment, around 5-10 % of patients still develop delayed union and nonunion. Evidence has increasingly shown that abnormal expression of long noncoding RNAs is closely related to the occurrence and development of various diseases including fracture healing. However, evidence regarding the effect of MALAT1 on fracture healing remains limited.
In this study, we attempt to explore the role of MALAT1 during the process of femoral neck fracture healing and elucidate the underlying mechanism of this disease.
We first detect the expression of lncRNAs in serums from 3 pairs of patients with delayed femoral neck fracture healing and healthy volunteers using lncRNA microarray. And the expression of long noncoding RNA MALAT1 in serums and LPS-treated MG-63 cells was measured using qRT-PCR. CCK-8 assay, cell migration and qRT-PCR were applied to the role of MALAT1 knockdown in LPS-treated MG-63 cells. ELISA was used for the measurement of inflammatory cytokines in serums of patients and healthy volunteers. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism.
MALAT1 expression was up-regulated in serum of patients with delayed union of femoral neck fracture. MALAT1 knockdown promoted cell viability and migration, reduced inflammation in LPS-treated MG-63 cells. The bioinformatics analysis showed MALAT1 acts as a molecular sponge for miR-212. And SOX6 was a target of miR-212. Besides, MALAT1 knockdown suppressed SOX6 expression via targeting miR-212 in LPS-treated MG-63 cells.
These data suggest MALAT1 knockdown promoted the biological behavior of LPS-treated MG-63 cells via sponging miR-212, which may provide a new therapeutic avenue for delayed union of femoral neck fracture.
大多数骨折经治疗后可愈合,但仍有 5-10%的患者会出现延迟愈合和不愈合。越来越多的证据表明,长链非编码 RNA 的异常表达与包括骨折愈合在内的各种疾病的发生和发展密切相关。然而,关于 MALAT1 对骨折愈合影响的证据仍然有限。
本研究旨在探讨 MALAT1 在股骨颈骨折愈合过程中的作用,并阐明其发病机制。
我们首先采用 lncRNA 微阵列检测 3 对股骨颈延迟愈合患者和健康志愿者血清中 lncRNA 的表达情况。采用 qRT-PCR 检测血清和 LPS 处理的 MG-63 细胞中长链非编码 RNA MALAT1 的表达。采用 CCK-8 法、细胞迁移实验和 qRT-PCR 检测 MALAT1 敲低对 LPS 处理的 MG-63 细胞的作用。采用 ELISA 法检测患者和健康志愿者血清中炎症细胞因子的含量。通过生物信息学分析和挽救实验探讨其作用机制。
延迟愈合的股骨颈骨折患者血清中 MALAT1 表达上调。MALAT1 敲低促进 LPS 处理的 MG-63 细胞的细胞活力和迁移,降低炎症反应。生物信息学分析表明,MALAT1 作为 miR-212 的分子海绵。SOX6 是 miR-212 的靶基因。此外,MALAT1 敲低通过靶向 miR-212 抑制 LPS 处理的 MG-63 细胞中 SOX6 的表达。
这些数据表明,MALAT1 敲低通过海绵吸附 miR-212 促进 LPS 处理的 MG-63 细胞的生物学行为,这可能为股骨颈延迟愈合提供新的治疗途径。