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Войти в исследования Orthopedic research and reviews · 2026
Multi-Omics Bioinformatic Analyses Linking LOXL4 with Spondylolisthesis.
СтатьяНазвание и аннотация: Перевод в очереди
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Wang Hui, Niu Peng, Yang Xiu, Lin Xin, Li Jinquan, Wu Guangyin, Sun Xiaotang, Huang Jianghu, Lin Feiyue
Аннотация
PURPOSE: Spondylolisthesis is a spinal disorder characterized by abnormal vertebral displacement, primarily affecting the lumbar region. Understanding the genetic factors underlying its progression is critical.
PATIENTS AND METHODS: This study aimed to identify key genes influencing spondylolisthesis progression. The summary-data-based Mendelian randomization (SMR) analysis was conducted to evaluate gene expression quantitative trait (eQTL) and DNA methylation QTL (mQTL) data that were causally associated with spondylolisthesis. Subsequently, key genes were discerned by Bayesian colocalization analysis. To validate the findings, Quantitative real time polymerase chain reaction (qRT-PCR) experiments were conducted using human osteosarcoma cells (SW-1353). Additionally, enrichment analysis, small molecule compounds prediction and molecular docking were performed to investigate how the key genes might impact spondylolisthesis.
RESULTS: SMR analysis identified 841 cis-eQTLs and 3,224 mQTLs potentially linked to spondylolisthesis (P < 0.05). Bayesian colocalization revealed LOXL4 as a key gene, with posterior probabilities (PPH4) exceeding 0.90 for both eQTL (ENSG00000138131) and mQTL (cg09335911). LOXL4 is implicated in pathways like "protein oxidation" and "collagen-containing extracellular matrix", which are critical for tissue integrity. Molecular docking suggested that LOXL4 binds strongly to estradiol and progesterone, pointing to a potential mechanism of hormonal regulation in spondylolisthesis. However, this remains a hypothesis requiring further experimental validation. Additionally, qRT-PCR experiments in hydrogen peroxide-treated SW1353cells showed that LOXL4 expression changes were consistent with our bioinformatics predictions, although this in vitro model may not fully reflect the gene's role in spondylolisthesis.
CONCLUSION: This findings suggest LOXL4 as a candidate gene involved in spondylolisthesis progression and a potential therapeutic target. Nevertheless, out results are preliminary and further research is needed to confirm LOXL4's role in this condition.
PATIENTS AND METHODS: This study aimed to identify key genes influencing spondylolisthesis progression. The summary-data-based Mendelian randomization (SMR) analysis was conducted to evaluate gene expression quantitative trait (eQTL) and DNA methylation QTL (mQTL) data that were causally associated with spondylolisthesis. Subsequently, key genes were discerned by Bayesian colocalization analysis. To validate the findings, Quantitative real time polymerase chain reaction (qRT-PCR) experiments were conducted using human osteosarcoma cells (SW-1353). Additionally, enrichment analysis, small molecule compounds prediction and molecular docking were performed to investigate how the key genes might impact spondylolisthesis.
RESULTS: SMR analysis identified 841 cis-eQTLs and 3,224 mQTLs potentially linked to spondylolisthesis (P < 0.05). Bayesian colocalization revealed LOXL4 as a key gene, with posterior probabilities (PPH4) exceeding 0.90 for both eQTL (ENSG00000138131) and mQTL (cg09335911). LOXL4 is implicated in pathways like "protein oxidation" and "collagen-containing extracellular matrix", which are critical for tissue integrity. Molecular docking suggested that LOXL4 binds strongly to estradiol and progesterone, pointing to a potential mechanism of hormonal regulation in spondylolisthesis. However, this remains a hypothesis requiring further experimental validation. Additionally, qRT-PCR experiments in hydrogen peroxide-treated SW1353cells showed that LOXL4 expression changes were consistent with our bioinformatics predictions, although this in vitro model may not fully reflect the gene's role in spondylolisthesis.
CONCLUSION: This findings suggest LOXL4 as a candidate gene involved in spondylolisthesis progression and a potential therapeutic target. Nevertheless, out results are preliminary and further research is needed to confirm LOXL4's role in this condition.