CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1

Jokoji, Go; Maeda, Shingo; Oishi, Kazuki; Ijuin, Toshiro; Nakajima, Masahiro; Tawaratsumida, Hiroki; Kawamura, Ichiro; Tominaga, Hiroyuki; Taketomi, Eiji; Ikegawa, Shiro; Taniguchi, Noboru

doi:10.1016/j.jbc.2021.100994

Cited by 9 publications

(10 citation statements)

References 46 publications

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“…Aggrecan, a cartilage-specific proteoglycan core protein, also plays a key role in articular cartilage and joint function [41]. In the process of chondrocyte differentiation, COL2A1 was expressed significantly in the early stage of the differentiation process, while ACAN was expressed at the late stage, indicating a cartilage maturation [42,43]. According to the current results, COL2A1 is upregulated, but ACAN expression is suppressed on the GlyCVD-BCC surface.…”

Section: Gene Expression Of Hbmscs On the Hybrid Nanostructuressupporting

confidence: 55%

“…COL2A1 is a crucial gene expressed in the early stage of chondrocyte differentiation of MSCs, which in turn generates type II collagen, the main protein of the cartilage ECM [42]. Type II collagen plays a critical role in articular cartilage due to its elasticity in joint function [41].…”

Section: Gene Expression Of Hbmscs On the Hybrid Nanostructuresmentioning

confidence: 99%

“…According to the current results, COL2A1 is upregulated, but ACAN expression is suppressed on the GlyCVD-BCC surface. hBMSCs could be stimulated into pre-chondrocyte-like cells on the GlyCVD-BCC surface, but these cells are far from mature [42,43].…”

Section: Gene Expression Of Hbmscs On the Hybrid Nanostructuresmentioning

confidence: 99%

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Hybrid Surface Nanostructures Using Chemical Vapor Deposition and Colloidal Self-Assembled Patterns for Human Mesenchymal Stem Cell Culture—A Preliminary Study

et al. 2022

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Surface coatings are critical in biomaterials and biomedical devices. Chemical vapor deposition (CVD) is a well-known technology for the generation of thin films on a surface. However, the granular structures produced using CVD are rare. Recently, we used PPX-C, an excellent insulating material, for granular structure coating using CVD. Colloidal self-assembly is also a well-established method to generate granular structures named colloidal self-assembled patterns (cSAPs). In this study, we combined these two technologies to generate hierarchical granular structures and tested the biophysical effect of these hybrid surfaces on human bone marrow mesenchymal stem cells (hBMSCs). Two CVD-derived granular structures were made using water or glycerin droplets (i.e., CVD or GlyCVD surfaces). Water drops generate porous particles, while glycerin drops generate core–shell particles on the surface. These particles were dispersed randomly on the surface with sizes ranging from 1 to 20 μm. These CVD surfaces were hydrophobic (WCA ~ 80–110 degrees). On the other hand, a binary colloidal crystal (BCC), one type of cSAPs, composed of 5 μm Si and 400 nm carboxylated polystyrene (PSC) particles, had a close-packed structure and a hydrophilic surface (WCA ~ 45 degrees). The hybrid surfaces (i.e., CVD-BCC and GlyCVD-BCC) were smooth (Ra ~ 1.1–1.5 μm) and hydrophilic (WCA ~ 50 degrees), indicating a large surface coverage of BCC dominating the surface property. The hybrid surfaces were expected to be slightly negatively charged due to naturally charged CVD particles and negatively charged BCC particles. Cell adhesion was reduced on the hybrid surfaces, leading to an aggregated cell morphology, without reducing cell activity, compared to the flat control after 5 days. qPCR analysis showed that gene expression of type II collagen (COL2) was highly expressed on the GlyCVD-BCC without chemical induction after 3 and 14 days compared to the flat control. This proof-of-concept study demonstrates the potential of combining two technologies to make hybrid structures that can modulate stem cell attachment and differentiation.

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Section: Gene Expression Of Hbmscs On the Hybrid Nanostructuressupporting

confidence: 55%

Section: Gene Expression Of Hbmscs On the Hybrid Nanostructuresmentioning

confidence: 99%

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Hybrid Surface Nanostructures Using Chemical Vapor Deposition and Colloidal Self-Assembled Patterns for Human Mesenchymal Stem Cell Culture—A Preliminary Study

et al. 2022

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“…Recent studies had reported the role of CDC5L in bone development. CDC5L was expressed in chondrocytes proliferating from mouse embryonic bone growth plates, and CDC5L mediates the promotion or inhibition of pre-mRNA splicing of early cartilage genes (Sox9 and Col2a1) or Wee1, respectively (Jokoji et al, 2021). CUL1 and CXCL10 were also frequently reported in immune regulation (Sorrentino et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes associated with osteoporosis development by comprehensive bioinformatics analysis

et al. 2023

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Osteoporosis (OP) is a systemic bone disease caused by various factors, including, the decrease of bone density and quality, the destruction of bone microstructure, and the increase of bone fragility. It is a disease with a high incidence in a large proportion of the world’s elderly population. However, osteoporosis lacks obvious symptoms and sensitive biomarkers. Therefore, it is extremely urgent to discover and identify disease-related biomarkers for early clinical diagnosis and effective intervention for osteoporosis. In our study, the Linear Models for Microarray Data (LIMMA) tool was used to screen differential expressed genes from transcriptome sequencing data of OP blood samples downloaded from the GEO database, and cluster Profiler was used for enriching analysis of differently expressed genes. In order to analyzed the relevance of gene modules, clinical symptoms, and the most related module setting genes associated with disease progression, we adapted Weighted Gene Co-expression Network Analysis (WGCNA) to screen and analyze the related pathways and relevant molecules. We used the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to construct protein interaction network of key modules, and Cytoscape software was used to complete network visualization and screen of core genes in the network. Various plug-in algorithms of cytoHubba were used to identify key genes of OP. Finally, correlation analysis and single-gene gene probe concentration analysis (GSEA) analysis were performed for each core gene. Results of a total of 8 key genes that were closely related to the occurrence and development of OP were screened out, which provided a brand-new idea for the clinical diagnosis and early prevention of OP. Quantitative real-time PCR (qRT-PCR) was performed for validation, the expression levels of CUL1, PTEN and STAT1 genes in the OS group were significantly higher than in the non-OS groups. Receiver operating characteristic analysis demonstrated that CUL1, PTEN and STAT1 displayed considerable diagnostic accuracy for OS.

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“…When the cell confluence reached 80%, the cells were passaged at a ratio of 1:3. According to literature, cells derived from OPLL mainly consist of fibroblasts, osteoblasts, and chondrocytes [ 39 , 40 ]. In this article, we define these cells as OPLL cells.…”

Section: Methodsmentioning

confidence: 99%

Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating the mTOR pathway in ossification of the posterior longitudinal ligament

et al. 2022

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Background Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease whose pathogenesis is still unclear, and there are no effective cures or prevention methods. Exosomal miRNA plays an important role in the osteogenesis of ectopic bone. Therefore, we focused on the downregulation of miR-140-5p in OPLL cell-derived exosomes to explore the mechanism by which exosomal miR-140-5p inhibits osteogenesis in OPLL. Results Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly downregulated. Confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified that exosomal miR-140-5p inhibited the osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of the IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited ectopic bone formation in mice as assessed by micro-CT and immunohistochemistry. Conclusions We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.

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CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1

Cited by 9 publications

References 46 publications

Hybrid Surface Nanostructures Using Chemical Vapor Deposition and Colloidal Self-Assembled Patterns for Human Mesenchymal Stem Cell Culture—A Preliminary Study

Hybrid Surface Nanostructures Using Chemical Vapor Deposition and Colloidal Self-Assembled Patterns for Human Mesenchymal Stem Cell Culture—A Preliminary Study

Identification of hub genes associated with osteoporosis development by comprehensive bioinformatics analysis

Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating the mTOR pathway in ossification of the posterior longitudinal ligament

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