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CTSD upregulation as a key driver of spinal ligament abnormalities in spinal stenosis.
Li, Lei; Zheng, Zhen-Zhong; Jiang, Jia-Jiong; Chen, Jia-Lin; Jiang, Bin; Li, Ya-Wei; Dai, Yu-Liang; Wang, Bing.
Afiliación
  • Li L; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Digital Spine Research Institute, Central South University, Changsha, China.
  • Zheng ZZ; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Digital Spine Research Institute, Central South University, Changsha, China.
  • Jiang JJ; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Digital Spine Research Institute, Central South University, Changsha, China.
  • Chen JL; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Digital Spine Research Institute, Central South University, Changsha, China.
  • Jiang B; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Digital Spine Research Institute, Central South University, Changsha, China.
  • Li YW; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Digital Spine Research Institute, Central South University, Changsha, China.
  • Dai YL; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Digital Spine Research Institute, Central South University, Changsha, China.
  • Wang B; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Digital Spine Research Institute, Central South University, Changsha, China. Electronic address: wbxyeyy@csu.edu.cn.
Bone ; 186: 117174, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38917962
ABSTRACT
Spinal stenosis (SS) is frequently caused by spinal ligament abnormalities, such as ossification and hypertrophy, which narrow the spinal canal and compress the spinal cord or nerve roots, leading to myelopathy or sciatic symptoms; however, the underlying pathological mechanism is poorly understood, hampering the development of effective nonsurgical treatments. Our study aims to investigate the role of co-expression hub genes in patients with spinal ligament ossification and hypertrophy. To achieve this, we conducted an integrated analysis by combining RNA-seq data of ossification of the posterior longitudinal ligament (OPLL) and microarray profiles of hypertrophy of the ligamentum flavum (HLF), consistently pinpointing CTSD as an upregulated hub gene in both OPLL and HLF. Subsequent RT-qPCR and IHC assessments confirmed the heightened expression of CTSD in human OPLL, ossification of the ligamentum flavum (OLF), and HLF samples. We observed an increase in CTSD expression in human PLL and LF primary cells during osteogenic differentiation, as indicated by western blotting (WB). To assess CTSD's impact on osteogenic differentiation, we manipulated its expression levels in human PLL and LF primary cells using siRNAs and lentivirus, as demonstrated by WB, ALP staining, and ARS. Our findings showed that suppressing CTSD hindered the osteogenic differentiation potential of PLL and LF cells, while overexpressing CTSD activated osteogenic differentiation. These findings identify CTSD as a potential therapeutic target for treating spinal stenosis associated with spinal ligament abnormalities.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estenosis Espinal / Regulación hacia Arriba / Osificación del Ligamento Longitudinal Posterior / Ligamento Amarillo Límite: Humans / Male Idioma: En Revista: Bone Asunto de la revista: METABOLISMO / ORTOPEDIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estenosis Espinal / Regulación hacia Arriba / Osificación del Ligamento Longitudinal Posterior / Ligamento Amarillo Límite: Humans / Male Idioma: En Revista: Bone Asunto de la revista: METABOLISMO / ORTOPEDIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos