Amri Raja, Chelly Ameni, Ayedi Mariem, Rebaii Mohamed Ali, Aifa Sami, Masmoudi Sabeur, Keskes Hassib
Research Laboratory Cell Therapy and Experimental Musculoskeletal System, Faculty of Medicine, Sfax, Tunisia.
Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, Sfax, Tunisia.
Bone Joint Res. 2024 Feb 19;13(2):83-90. doi: 10.1302/2046-3758.132.BJR-2023-0023.R2.
The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.
A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).
We found that RANKL and RUNX2 gene expression was upregulated more in recurrent than in non-recurrent GCTB tissues, while OPG gene expression was downregulated more in recurrent than in non-recurrent GCTB tissues. Additionally, we proved that changes in DNA methylation contribute to upregulating the expression of RANKL and downregulating the expression of OPG, which are critical for bone homeostasis and GCTB development.
Our results suggest that the overexpression of RANKL/RUNX2 and the lower expression of OPG are associated with recurrence in GCTB patients.
本研究调查骨巨细胞瘤(GCTB)患者中核因子κB受体激活剂配体(RANKL)、骨保护素(OPG)和 runt 相关转录因子 2(RUNX2)基因表达与肿瘤复发的关系。我们还旨在研究 CpG 甲基化对 RANKL 和 OPG 转录水平的影响。
共分析 32 例 GCTB 组织样本,通过定量聚合酶链反应(qPCR)评估 RANKL、OPG 和 RUNX2 的表达。还通过定量甲基化特异性聚合酶链反应(qMSP)评估 RANKL 和 OPG 的甲基化状态。
我们发现,与非复发性 GCTB 组织相比,复发性 GCTB 组织中 RANKL 和 RUNX2 基因表达上调更明显,而复发性 GCTB 组织中 OPG 基因表达下调更明显。此外,我们证明 DNA 甲基化的变化有助于上调 RANKL 的表达并下调 OPG 的表达,这对骨稳态和 GCTB 的发展至关重要。
我们的结果表明,RANKL/RUNX2 的过表达和 OPG 的低表达与 GCTB 患者的复发有关。