دورية أكاديمية
CTSD upregulation as a key driver of spinal ligament abnormalities in spinal stenosis.
| العنوان: | CTSD upregulation as a key driver of spinal ligament abnormalities in spinal stenosis. |
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| المؤلفون: | 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. |
| المصدر: | Bone [Bone] 2024 Sep; Vol. 186, pp. 117174. Date of Electronic Publication: 2024 Jun 24. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 8504048 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2763 (Electronic) Linking ISSN: 18732763 NLM ISO Abbreviation: Bone Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York : Elsevier Science Original Publication: Elmsford, NY : Pergamon Press, c1985- |
| مواضيع طبية MeSH: | Ligamentum Flavum*/pathology , Ligamentum Flavum*/metabolism , Ossification of Posterior Longitudinal Ligament*/genetics , Ossification of Posterior Longitudinal Ligament*/pathology , Ossification of Posterior Longitudinal Ligament*/metabolism , Spinal Stenosis*/pathology , Spinal Stenosis*/genetics , Spinal Stenosis*/metabolism , Up-Regulation*/genetics, Humans ; Male ; Cell Differentiation/genetics ; Longitudinal Ligaments/pathology ; Longitudinal Ligaments/metabolism ; Osteogenesis/genetics |
| مستخلص: | 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. Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have influenced the work reported in this paper. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: CTSD; Ligamentum flavum hypertrophy; Ossification of the ligamentum flavum; Ossification of the posterior longitudinal ligament; Osteogenesis; Spinal stenosis |
| المشرفين على المادة: | EC 3.4.23.5 (CTSD protein, human) |
| تواريخ الأحداث: | Date Created: 20240625 Date Completed: 20240706 Latest Revision: 20240718 |
| رمز التحديث: | 20240718 |
| DOI: | 10.1016/j.bone.2024.117174 |
| PMID: | 38917962 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1873-2763 |
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| DOI: | 10.1016/j.bone.2024.117174 |