LncRNA HCG18 regulates the progression of spinal tuberculosis by modulating the hsa-miR-146a-5p/TGF-β1/SMADs pathway

Abstract Spinal tuberculosis is the most common extrapulmonary tuberculosis, characterized by intervertebral disc destruction, which seriously affects people’s quality of life. Recent studies have suggested that the TGF-β1/SMADs signaling pathway plays an important regulatory role in the process of...

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Main Authors: Feng Li, Hongdong Tan, Xiao Zhang, Xiaodong Zhao, Xiaopeng Li, Gaoyang Chen
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Journal of Orthopaedic Surgery and Research
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Online Access:https://doi.org/10.1186/s13018-025-05810-3
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author Feng Li
Hongdong Tan
Xiao Zhang
Xiaodong Zhao
Xiaopeng Li
Gaoyang Chen
author_facet Feng Li
Hongdong Tan
Xiao Zhang
Xiaodong Zhao
Xiaopeng Li
Gaoyang Chen
author_sort Feng Li
collection DOAJ
description Abstract Spinal tuberculosis is the most common extrapulmonary tuberculosis, characterized by intervertebral disc destruction, which seriously affects people’s quality of life. Recent studies have suggested that the TGF-β1/SMADs signaling pathway plays an important regulatory role in the process of intervertebral disc destruction caused by spinal tuberculosis. However, the abnormal TGF-β1/SMADs signaling pathway in spinal tuberculosis is not fully understood. Herein, we found for the first time that HCG18 was significantly upregulated in spinal tuberculosis nucleus pulposus clinical samples and confirmed that HCG18 negatively regulates the proliferation and migration ability of nucleus pulposus cells (NPCs). In vitro experiments further suggest that overexpression of HCG18 can significantly promote TGF-β1/SMADs pathway activity and inhibit proliferation, migration, and apoptosis of NPCs, an effect which can be reversed by overexpressing hsa-miR-146a-5p. On the contrary, knocking down HCG18 yields the opposite result. In vivo experiments suggest that knocking down HCG18 can significantly alleviate the destruction of the nucleus pulposus in rats with spinal tuberculosis by inhibiting the activity of the TGF-β1/SMADs pathway. In summary, our research suggests that HCG18 can promote the progression of spinal tuberculosis by alleviating the inhibitory effect of hsa-miR-146a-5p on the TGF-β1/SMADs pathway. This study provides new insights into the occurrence and development of spinal tuberculosis, as well as new strategies for the prevention and treatment of spinal tuberculosis.
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spelling doaj-art-3e9e7ee8f4f94c60a721e2f76e9b835a2025-08-20T02:34:19ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-05-0120111210.1186/s13018-025-05810-3LncRNA HCG18 regulates the progression of spinal tuberculosis by modulating the hsa-miR-146a-5p/TGF-β1/SMADs pathwayFeng Li0Hongdong Tan1Xiao Zhang2Xiaodong Zhao3Xiaopeng Li4Gaoyang Chen5Department of Spine Surgery, The First Affiliated Hospital of Shandong Second Medical University (Weifang People’s Hospital)Department of Orthopedic Surgery, Shandong Public Health Clinical CenterDepartment of Spine Surgery, The First Affiliated Hospital of Shandong Second Medical University (Weifang People’s Hospital)Department of Spine Surgery, The First Affiliated Hospital of Shandong Second Medical University (Weifang People’s Hospital)Department of Spine Surgery, The First Affiliated Hospital of Shandong Second Medical University (Weifang People’s Hospital)Division of Hand & Foot and Microvascular Surgery, Department of Orthopedic Surgery, Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People’s Hospital)Abstract Spinal tuberculosis is the most common extrapulmonary tuberculosis, characterized by intervertebral disc destruction, which seriously affects people’s quality of life. Recent studies have suggested that the TGF-β1/SMADs signaling pathway plays an important regulatory role in the process of intervertebral disc destruction caused by spinal tuberculosis. However, the abnormal TGF-β1/SMADs signaling pathway in spinal tuberculosis is not fully understood. Herein, we found for the first time that HCG18 was significantly upregulated in spinal tuberculosis nucleus pulposus clinical samples and confirmed that HCG18 negatively regulates the proliferation and migration ability of nucleus pulposus cells (NPCs). In vitro experiments further suggest that overexpression of HCG18 can significantly promote TGF-β1/SMADs pathway activity and inhibit proliferation, migration, and apoptosis of NPCs, an effect which can be reversed by overexpressing hsa-miR-146a-5p. On the contrary, knocking down HCG18 yields the opposite result. In vivo experiments suggest that knocking down HCG18 can significantly alleviate the destruction of the nucleus pulposus in rats with spinal tuberculosis by inhibiting the activity of the TGF-β1/SMADs pathway. In summary, our research suggests that HCG18 can promote the progression of spinal tuberculosis by alleviating the inhibitory effect of hsa-miR-146a-5p on the TGF-β1/SMADs pathway. This study provides new insights into the occurrence and development of spinal tuberculosis, as well as new strategies for the prevention and treatment of spinal tuberculosis.https://doi.org/10.1186/s13018-025-05810-3Spinal tuberculosisIntervertebral disc destructionHCG18SMADs signaling pathwayhsa-miR-146a-5p
spellingShingle Feng Li
Hongdong Tan
Xiao Zhang
Xiaodong Zhao
Xiaopeng Li
Gaoyang Chen
LncRNA HCG18 regulates the progression of spinal tuberculosis by modulating the hsa-miR-146a-5p/TGF-β1/SMADs pathway
Journal of Orthopaedic Surgery and Research
Spinal tuberculosis
Intervertebral disc destruction
HCG18
SMADs signaling pathway
hsa-miR-146a-5p
title LncRNA HCG18 regulates the progression of spinal tuberculosis by modulating the hsa-miR-146a-5p/TGF-β1/SMADs pathway
title_full LncRNA HCG18 regulates the progression of spinal tuberculosis by modulating the hsa-miR-146a-5p/TGF-β1/SMADs pathway
title_fullStr LncRNA HCG18 regulates the progression of spinal tuberculosis by modulating the hsa-miR-146a-5p/TGF-β1/SMADs pathway
title_full_unstemmed LncRNA HCG18 regulates the progression of spinal tuberculosis by modulating the hsa-miR-146a-5p/TGF-β1/SMADs pathway
title_short LncRNA HCG18 regulates the progression of spinal tuberculosis by modulating the hsa-miR-146a-5p/TGF-β1/SMADs pathway
title_sort lncrna hcg18 regulates the progression of spinal tuberculosis by modulating the hsa mir 146a 5p tgf β1 smads pathway
topic Spinal tuberculosis
Intervertebral disc destruction
HCG18
SMADs signaling pathway
hsa-miR-146a-5p
url https://doi.org/10.1186/s13018-025-05810-3
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