The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis

Myngbay, Askhat; Manarbek, Limara; Ludbrook, Steve; Kunz, Jeannette

doi:10.3390/ijms22052426

Cited by 18 publications

(11 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RA is a chronic inflammatory disease with the feature of Treg/Th17 imbalance, resulting in cartilage degradation and bone erosion within both small and large joints ( 15 ). The exact cause of RA remains unknown, posing a challenge to the diagnosis and treatment for RA ( 16 ).…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Immunoregulation by Artemisinin and Its Derivatives: A New Role for Old Antimalarial Drugs

Qiu

Liu

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Artemisinin and its derivatives (ARTs) are known as conventional antimalarial drugs with clinical safety and efficacy. Youyou Tu was awarded a Nobel Prize in Physiology and Medicine due to her discovery of artemisinin and its therapeutic effects on malaria. Apart from antimalarial effects, mounting evidence has demonstrated that ARTs exert therapeutic effects on inflammation and autoimmune disorders because of their anti-inflammatory and immunoregulatory properties. In this aspect, tremendous progress has been made during the past five to seven years. Therefore, the present review summarizes recent studies that have explored the anti-inflammatory and immunomodulatory effects of ARTs on autoimmune diseases and transplant rejection. In this review, we also discuss the cellular and molecular mechanisms underlying the immunomodulatory effects of ARTs. Recent preclinical studies will help lay the groundwork for clinical trials using ARTs to treat various immune-based disorders, especially autoimmune diseases.

show abstract

Section: Rheumatoid Arthritismentioning

confidence: 99%

Immunoregulation by Artemisinin and Its Derivatives: A New Role for Old Antimalarial Drugs

Qiu

Liu

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Futhermore, transcript levels of the glycoprotein CTHRC1 were reduced by H19 silencing. This protein has been widely described to promote cell migration [55] and abundant expression levels of CTHRC1 are detected in the bone matrix during embryogenesis and in adult mice [56]. Ablation of CTHRC1 results in the impairment of bone formation [57], while increased levels of CTHRC1 stimulate differentiation and mineralization of osteoprogenitor cells [57,58].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA H19 regulates matrisome signature and impacts cell behavior on MSC-engineered extracellular matrices

et al. 2023

View full text Add to dashboard Cite

Background The vast and promising class of long non-coding RNAs (lncRNAs) has been under investigation for distinct therapeutic applications. Nevertheless, their role as molecular drivers of bone regeneration remains poorly studied. The lncRNA H19 mediates osteogenic differentiation of Mesenchymal Stem/Stromal Cells (MSCs) through the control of intracellular pathways. However, the effect of H19 on the extracellular matrix (ECM) components is still largely unknown. This research study was designed to decode the H19-mediated ECM regulatory network, and to reveal how the decellularized siH19-engineered matrices influence MSC proliferation and fate. This is particularly relevant for diseases in which the ECM regulation and remodeling processes are disrupted, such as osteoporosis. Methods Mass spectrometry-based quantitative proteomics analysis was used to identify ECM components, after oligonucleotides delivery to osteoporosis-derived hMSCs. Moreover, qRT-PCR, immunofluorescence and proliferation, differentiation and apoptosis assays were performed. Engineered matrices were decellularized, characterized by atomic force microscopy and repopulated with hMSC and pre-adipocytes. Clinical bone samples were characterized by histomorphometry analysis. Results Our study provides an in-depth proteome-wide and matrisome-specific analysis of the ECM proteins controlled by the lncRNA H19. Using bone marrow-isolated MSC from patients with osteoporosis, we identified fibrillin-1 (FBN1), vitronectin (VTN) and collagen triple helix repeat containing 1 (CTHRC1), among others, as having different pattern levels following H19 silencing. Decellularized siH19-engineered matrices are less dense and have a decreased collagen content compared with control matrices. Repopulation with naïve MSCs promotes a shift towards the adipogenic lineage in detriment of the osteogenic lineage and inhibits proliferation. In pre-adipocytes, these siH19-matrices enhance lipid droplets formation. Mechanistically, H19 is targeted by miR-29c, whose expression is decreased in osteoporotic bone clinical samples. Accordingly, miR-29c impacts MSC proliferation and collagen production, but does not influence ALP staining or mineralization, revealing that H19 silencing and miR-29c mimics have complementary but not overlapping functions. Conclusion Our data suggest H19 as a therapeutic target to engineer the bone ECM and to control cell behavior.

show abstract

“…This could also modulate how secreted growth factors (i.e.,TGFb and Wnt) are sequestered by the matrix in breast cancer cells [ 71 ]. CTHRC1 expression is associated with metastasis to the bone [ 72 ]. In breast cancer patients with high periostin, the risk of bone metastases is enhanced by elevated CTHRC1 expression [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

A pan-cancer analysis of matrisome proteins reveals CTHRC1 and a related network as major ECM regulators across cancers

2022

View full text Add to dashboard Cite

The extracellular matrix in the tumour microenvironment can regulate cancer cell growth and progression. A pan-cancer analysis of TCGA data from 30 cancer types, identified the top 5% of matrisome genes with amplifications or deletions in their copy number, that affect their expression and cancer survival. A similar analysis of matrisome genes in individual cancers identified CTHRC1 to be significantly altered. CTHRC1, a regulator of collagen synthesis, was identified as the most prominently upregulated matrisome gene of interest across cancers. Differential gene expression analysis identified 19 genes whose expression is increased with CTHRC1. STRING analysis of these genes classified them as ‘extracellular’, involved most prominently in ECM organization and cell adhesion. KEGG analysis showed their involvement in ECM-receptor and growth factor signalling. Cytohubba analysis of these genes revealed 13 hub genes, of which MMP13, POSTN, SFRP4, ADAMTS16 and FNDC1 were significantly altered in their expression with CTHRC1 and seen to affect survival across cancers. This could in part be mediated by their overlapping roles in regulating ECM (collagen or fibronectin) expression and organisation. In breast cancer tumour samples CTHRC1 protein levels are significantly upregulated with POSTN and MMP13, further supporting the need to evaluate their crosstalk in cancers.

show abstract

The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis

Cited by 18 publications

References 88 publications

Immunoregulation by Artemisinin and Its Derivatives: A New Role for Old Antimalarial Drugs

Immunoregulation by Artemisinin and Its Derivatives: A New Role for Old Antimalarial Drugs

Long non-coding RNA H19 regulates matrisome signature and impacts cell behavior on MSC-engineered extracellular matrices

A pan-cancer analysis of matrisome proteins reveals CTHRC1 and a related network as major ECM regulators across cancers

Contact Info

Product

Resources

About