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Single-cell RNA sequencing reveals the CRTAC1+ population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1+ macrophage

ABSTRACT: Degenerative spinal stenosis is a chronic disease that affects the spinal ligaments and associated bones, resulting in back pain and disorders of the limbs among the elderly population. There are few preventive strategies for such ligament degeneration. We here aimed to establish a comprehensive transcriptomic atlas of ligament tissues to identify high-priority targets for pharmaceutical treatment of ligament degeneration. Here, single-cell RNA sequencing was performed on six degenerative ligaments and three traumatic ligaments to understand tissue heterogeneity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271018 | GEO | 2024/07/31

REPOSITORIES: GEO

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Comprehensive proteomic comparison between native tendon and ligament and 3D tissue engineered tendon and ligament constructs

Project description:Tendons and ligaments are important biological structures in both humans and animals. They are part of dense connective tissue and are crucial to the functioning of the musculoskeletal system. However, they are commonly damaged due to age-related wear and tear, trauma or sports related incidents, which can lead to severe immobility for the individual and can lead to injury of other tissues and development of degenerative joint disease such as osteoarthritis. Tissue engineering can offer great potential in the treatment of tendon and ligament injury by seeking a biological replacement with fully regenerated autologenous tissue. This approach commonly involves an artificial ECM (scaffold) on which cell can proliferate and differentiate with subsequent new tissue generation. Fibrin is a natural scaffold with no expected toxic degradation or inflammatory reaction and can be used as an autologous scaffold for fibroblast from connective tissue to create a three dimensional structure. The purpose of this study was to compare the proteomic differences between native tendon, ligament and 3D tissue engineered tendon and ligament fibrin constructs.

2016-06-27 | PXD003094 | Pride

Altered extracellular matrix protein dynamics distinguishes canine ligament-derived stem cells from fibroblasts

Project description:Ligaments are prone to injury and degeneration in humans and animals, however the healing potential of ligament is poor and current treatment options lack effectiveness. Stem cell-based therapies hold potential for treatment of ligament injuries. This study aimed to characterise ligament-derived stem cell (LDSC) and ligament fibroblast populations as well as to identify specific niche components which could be used to promote the survival and function of LDSCs. LDSCs and ligament fibroblasts were isolated from canine cranial cruciate ligament and characterised for clonogenicity, multipotency and marker expression. The extracellular matrix (ECM) composition was characterised using a novel metabolic labelling and mass spectrometry approach. Both cell types demonstrated clonogenicity, with significant differences seen in colony size. Stem cell and tenogenic marker expression was increased in LDSCs compared with ligament fibroblasts, although this was only significant for the MSC marker CD73. Both cell types demonstrated multipotency, however this was more marked in LDSCs. A number of collagens, glycoproteins, proteoglycans and ECM regulators were identified in both the LDSC and ligament fibroblast niche using proteomics, with some differences between cell types, including collagens, decorin and fibronectin. Metabolic labelling of cells demonstrated unique turnover profiles for distinct ECM protein groups, with significant differences in new synthesis seen between cell types for a number of proteins, including collagen, decorin and elastin. In conclusion, different cell populations were observed in canine ligament with differences in niche composition and dynamics seen between the two cell types. These differences could be exploited to aid identification of LDSCs and to promote survival and function of LDSCs for potential therapeutic strategies.

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Gene profiling of the early healing rat medial collateral ligament

2013-06-06 | GSE47676 | GEO

Single-cell RNA sequencing reveals the CRTAC1+ population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1+ macrophage

Project description:Single-cell RNA sequencing reveals the CRTAC1+ population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1+ macrophage

| PRJNA1129430 | ENA

Experimental study on gene expression profile of medial meniscus after resection of anterior cruciate ligament and lateral collateral ligament

Project description:To explore the molecular mechanisms of meniscal degeneration after resection of anterior cruciate ligament and lateral collateral ligament, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential role in the development of meniscal degeneration. The anterior cruciate ligament (ACL) and lateral collateral ligament (LCL) of the right rear limbs of Wuzhishan minipig was resected at the same time, and the left rear limbs was sham operated. There were significant differences in gene expression between the two groups. A total of 893 differentially expressed genes were identified, of which 537 were upregulated and 356 were downregulated. This study indicated that several molecular mechanisms were implicated in the development of meniscal degeneration, thus improving our understanding of meniscal degeneration and offering molecular targets for future therapeutic advances.

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Gene profiling of the early healing rat medial collateral ligament

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2013-06-06 | E-GEOD-47676 | biostudies-arrayexpress

Effect of Cyclic stretching on the gene expression in human spinal ligament cells

Project description:Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by progressive ectopic bone formation in the spinal ligament. To identify the genes related to ectopic ossification of human spinal ligament affected by mechanical stress, analyses using cDNA microarray were carried out using cultured human spinal ligament cells that had been subjected to uniaxial cyclic stretching. cDNA microarrays revealed that ranges of distribution of both up- and down-regulated genes evoked by cyclic stretching were significantly wider in cells from than in non-OPLL cells. Keywords: mechanical-stress response

2006-08-09 | GSE5464 | GEO

single cell RNA sequencing of intra- and extra- articular ligaments in mice

Project description:Knee ligaments, the anterior cruciate ligament (ACL) and medial collateral ligament (MCL), have unique functions but distinct regeneration capacities. However, the landscape of cellular heterogeneity in ligaments remains unclear. Here we profile the transcriptional signatures of ACL and MCL cells using single-cell RNA-sequencing. These ligaments consist of three fibroblast types that express Col22a1, Col12a1, or Col14a1 but have distinct localizations in the tissue. In addition, we find substantial heterogeneity in Col12a1 and Col14a1 positive cell clusters when comparing the ACL and MCL. Furthermore, we identified aging related changes in both cell composition and gene expression in ligaments.

2022-11-14 | GSE194427 | GEO

Human POP analysis - Proteomics of Uterosacral Ligament Connective Tissue from Women With and Without Pelvic Organ Prolapse

Project description:Purpose: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study was to identify differentially expressed proteins in the uterosacral ligaments of women with and without pelvic organ prolapse and analyze their relationships to cellular mechanisms involved in the pathogenesis of pelvic organ prolapse. Experimental Design: Uterosacral ligament connective tissue from four patients with pelvic organ prolapse and four control women underwent iTRAQ analysis followed by Ingenuity Pathway Analysis of differentially expressed proteins. Differentially expressed proteins were valideated using western blot analysis. Results: A total of 1789 unique protein sequences were identified in the uterosacral ligament connective tissues. 88 proteins had expression levels that were significantly different between prolapse and control groups (≥1.2-fold). Ingenuity pathway analysis demonstrated 14 differentially expressed proteins that were associated with "Connective Tissue Function". Among them, fibromodulin(FMOD), Collagen alpha-1 (XIV) chain(COL14A1), Calponin-1 (CNN-1), Tenascin (TNC), and Galectin-1(LGALS1 appeared most likely to play a role in the etiology of pelvic organ prolapse. Conclusions and clinical relevence: We identified at least 6 proteins not previously associated with the pathogenesis of pelvic organ prolapse with biologic functions that suggest a plausible relationship to the disorder. These results may be helpful for furthering our understanding of the pathophysiological mechanisms of pelvic organ prolapse.

2018-12-10 | PXD011467 | Pride

Phenotypic analysis of conventional knockout mice lacking a protein responsible for ossification of the posterior longitudinal ligament

Project description:We found disease-specific proteins from serum proteomics of ossification of posterior longitudinal ligament, and made knockout mice. We discovered protein peculiar to a disease in serum of the ossification of posterior longitudinal ligament (OPLL), and, as a result of producing knockout mouse, we checked spinal ligament ossification and combination of diabetes and thought that it was a typical mouse and analyzed the sequence of the kidney organization.

2018-05-01 | GSE57590 | GEO

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