Suppression of CRLF1 promotes the chondrogenic differentiation of bone marrow-derived mesenchymal stem and protects cartilage tissue from damage in osteoarthritis via activation of miR-320

Xu, Hao; Ding, Changrong; Guo, Cuicui; Xiang, Shuai; Wang, Yingzhen; Luo, Bing; Xiang, Hongfei

doi:10.1186/s10020-021-00369-1

Cited by 11 publications

(7 citation statements)

References 24 publications

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“…CRLF1 and MFAP5 had lower total cell percentage expression in poly JIA FLS compared to oligo JIA FLS. Repression of CRLF1 expression causes mesenchymal stem cells to differentiate as chondrocytes [ 38 ]. MFAP5 promotes cell proliferation in tumors and interacts with the ERK/MMP signaling pathways [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis reveals heterogeneity of juvenile idiopathic arthritis fibroblast-like synoviocytes with implications for disease subtype

2022

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Background Fibroblast-like synoviocytes (FLS) play a crucial role in JIA pathogenesis; however, the mechanisms by which they contribute to disease progression are not well described. Previous studies demonstrated that rheumatoid arthritis FLS are heterogeneous, and subpopulations with transformed, aggressive phenotypes cause invasive and destructive disease activity. We employ single-cell RNA-sequencing (scRNA-seq) to investigate JIA FLS heterogeneity and gene expression that distinguishes JIA subtypes. Methods JIA FLS cell lines from three persistent oligoarticular, three pre-extension oligoarticular, and three polyarticular subtypes were cultured. scRNA-seq was performed by Genewiz according to 10 × Genomics Chromium protocols. SeuratR package was used for QC, analysis, and exploration of data. Results FLS are heterogeneous and have characteristics of fibroblasts, chondrocytes, and smooth muscle cells. The chondrocyte-like subpopulation is the predominant cell type and percentages of this subpopulation increase with disease severity. Despite overlapping subpopulations, the chondrocyte-like cells have unique genetic fingerprints that distinguish between JIA subtypes. LRRC15, GREM1, and GREM2 are overexpressed in chondrocyte-like cells from persistent oligoarticular JIA FLS compared to pre-extension oligoarticular JIA FLS. S100A4, TIMP3, and NBL1 are overexpressed in pre-extension oligoarticular JIA FLS compared to polyarticular JIA FLS. CRLF1, MFAP5, and TNXB are overexpressed in persistent oligoarticular JIA FLS compared to polyarticular JIA FLS. Conclusions We found biologically relevant differences in gene expression between JIA subtypes that support a critical role for FLS in pathogenesis. We also demonstrate that gene expression within the chondrocyte-like subpopulation can be used to distinguish between these subtypes.

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Section: Discussionmentioning

confidence: 99%

Single-cell analysis reveals heterogeneity of juvenile idiopathic arthritis fibroblast-like synoviocytes with implications for disease subtype

2022

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“…This evidence suggests that the CRLF1/CLCF1 complex may disrupt cartilage homeostasis and promote the progress of osteoarthritis. However, its function in chondrogenic differentiation remains unclear [113]. In ectopic bone formation induced by injection of BMP-2 into the muscle, expression of Crlf1 was induced 5-fold at day 5 after BMP-2 injection.…”

Section: Bone and Cartilagementioning

confidence: 99%

“…miR-320 was recently discovered as a negative regulator of osteoblast differentiation of hMSCs [117]. Xu et al [113] found that miR-320 is directly bound to the 3'UTR of CRLF1. Overexpression of CRLF1 inhibited BMSCs viability, induced apoptosis, and suppressed chondrogenic differentiation of BMSCs.…”

Section: Bone and Cartilagementioning

confidence: 99%

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CRLF1 and CLCF1 in Development, Health and Disease

Crisponi

Buers

Rutsch

2022

IJMS

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Cytokines and their receptors have a vital function in regulating various processes such as immune function, inflammation, haematopoiesis, cell growth and differentiation. The interaction between a cytokine and its specific receptor triggers intracellular signalling cascades that lead to altered gene expression in the target cell and consequent changes in its proliferation, differentiation, or activation. In this review, we highlight the role of the soluble type I cytokine receptor CRLF1 (cytokine receptor-like factor-1) and the Interleukin (IL)-6 cytokine CLCF1 (cardiotrophin-like cytokine factor 1) during development in physiological and pathological conditions with particular emphasis on Crisponi/cold-induced sweating syndrome (CS/CISS) and discuss new insights, challenges and possibilities arising from recent studies.

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“…Bone marrow mesenchymal stem cells (BMSCs) are nonhematopoietic stem cells with self-renewal ability and multiple differentiation potentials [1][2][3]. Major breakthroughs have been made in the use of BMSCs to solve neurological diseases, meniscus damage repair, and hematological diseases [4][5][6]. However, the transplantation effect of BMSCs is less obvious for treating ischemic and hypoxic diseases, such as avascular necrosis of the femoral head [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs

et al. 2022

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Bone marrow mesenchymal stem cells (BMSCs) have strong regenerative potential and show good application prospects for treating clinical diseases. However, in the process of BMSC transplantation for treating ischemic and hypoxic diseases, BMSCs have high rates of apoptosis in the hypoxic microenvironment of transplantation, which significantly affects the transplantation efficacy. Our previous studies have confirmed the key role of long non-coding RNA Tmem235 (LncRNA Tmem235) in the process of hypoxia-induced BMSC apoptosis and its downstream regulatory mechanism, but the upstream mechanism by which hypoxia regulates LncRNA Tmem235 expression to induce BMSC apoptosis is still unclear. Under hypoxic conditions, we found that the level of LncRNA Tmem235 promoter histone H3 lysine 27 trimethylation modification (H3K27me3) was significantly increased by CHIP-qPCR. Moreover, H3K27me3 cooperated with LncRNA Tmem235 promoter DNA methylation to inhibit the expression of LncRNA Tmem235 and promote apoptosis of BMSCs. To study the mechanism of hypoxia-induced modification of LncRNA Tmem235 promoter H3K27me3 in the hypoxia model of BMSCs, we detected the expression of H3K27 methylase and histone demethylase and found that only histone methylase enhancer of zeste homolog 2 (EZH2) expression was significantly upregulated. Knockdown of EZH2 significantly decreased the level of H3K27me3 modification in the LncRNA Tmem235 promoter. The EZH2 promoter region contains a hypoxia-responsive element (HRE) that interacts with hypoxia-inducible factor-1alpha (HIF-1α), which is overexpressed under hypoxic conditions, thereby promoting its overexpression. In summary, hypoxia promotes the modification of the LncRNA Tmem235 promoter H3K27me3 through the HIF-1α/EZH2 signaling axis, inhibits the expression of LncRNA Tmem235, and leads to hypoxic apoptosis of BMSCs. Our findings improve the regulatory mechanism of LncRNA Tmem235 during hypoxic apoptosis of BMSCs and provide a more complete theoretical pathway for targeting LncRNA to inhibit hypoxic apoptosis of BMSCs.

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Suppression of CRLF1 promotes the chondrogenic differentiation of bone marrow-derived mesenchymal stem and protects cartilage tissue from damage in osteoarthritis via activation of miR-320

Cited by 11 publications

References 24 publications

Single-cell analysis reveals heterogeneity of juvenile idiopathic arthritis fibroblast-like synoviocytes with implications for disease subtype

Single-cell analysis reveals heterogeneity of juvenile idiopathic arthritis fibroblast-like synoviocytes with implications for disease subtype

CRLF1 and CLCF1 in Development, Health and Disease

Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs

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