Valproic Acid-Induced CCN1 Promotes Osteogenic Differentiation by Increasing CCN1 Protein Stability through HDAC1 Inhibition in Tonsil-Derived Mesenchymal Stem Cells

Yu, Yeonsil; Oh, Se Young; Kim, Ha Yeong; Choi, Ji-Young; Jo, Sangmee Ahn; Jo, Inho

doi:10.3390/cells11030534

Cited by 15 publications

(6 citation statements)

References 47 publications

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“…CCN1, LAPTM5, and ArhGAP15 are among the most common genes. CCN1 is linked to HDAC1 inhibition 40 , and LAPTM5 has been identified as an mRNA signature for PTCL 41 . For ArhGAP15, one of its gene family, ArhGAP30, is associated with histone acetylation, which is known to facilitate p53 acetylation 42 .…”

Section: Resultsmentioning

confidence: 99%

Molecular data representation based on gene embeddings for cancer drug response prediction

Park,

Lee

2023

Sci Rep

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Cancer drug response prediction is a crucial task in precision medicine, but existing models have limitations in effectively representing molecular profiles of cancer cells. Specifically, when these models represent molecular omics data such as gene expression, they employ a one-hot encoding-based approach, where a fixed gene set is selected for all samples and omics data values are assigned to specific positions in a vector. However, this approach restricts the utilization of embedding-vector-based methods, such as attention-based models, and limits the flexibility of gene selection. To address these issues, our study proposes gene embedding-based fully connected neural networks (GEN) that utilizes gene embedding vectors as input data for cancer drug response prediction. The GEN allows for the use of embedding-vector-based architectures and different gene sets for each sample, providing enhanced flexibility. To validate the efficacy of GEN, we conducted experiments on three cancer drug response datasets. Our results demonstrate that GEN outperforms other recently developed methods in cancer drug prediction tasks and offers improved gene representation capabilities. All source codes are available at https://github.com/DMCB-GIST/GEN/.

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Section: Resultsmentioning

confidence: 99%

Molecular data representation based on gene embeddings for cancer drug response prediction

Park,

Lee

2023

Sci Rep

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“…Other groups were reported that adipose tissue-derived stem cells could also differentiate into neuronal cells by treating VPA [ 12 , 49 ]. Similarly, it has been reported that VPA has a potential as an agent of neurogenic differentiation via activating histone H3 core acetylation in embryonic stem cells [ 50 ] and osteogenic differentiation in tonsil-derived mesenchymal stem cells [ 51 ]. Animal studies have also shown that VPA treatment in the rat cerebral cortex induced differentiation via activation of the ERK-P21 Cip/WAFI pathway [ 45 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of HDAC inhibitors on neuroblastoma SH-SY5Y cell differentiation into mature neurons via the Wnt signaling pathway

et al. 2023

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Histone deacetylase (HDAC) inhibitors affect cell homeostasis, gene expression, and cell cycle progression and promote cell terminal differentiation or apoptosis. However, the effect of HDAC inhibition on SH-SY5Y cells, which are neuroblastoma cells capable of differentiating into neurons under specific conditions, such as in the presence of retinoic acid (RA), is unknown. In this study, we hypothesized that HDAC inhibitors induced the neuronal differentiation of SH-SY5Y cells. To test this hypothesis, we used phase contrast microscopy, immunocytochemistry (ICC), qPCR, and western blotting analysis. MS-275 and valproic acid (VPA), two HDAC inhibitors, were selected to evaluate neuronal differentiation. It was confirmed that cells treated with MS-275 or VPA differentiated into mature neurons, which were distinguished by bipolar or multipolar morphologies with elongated branches. In addition, the mRNA expression of neuronal markers (Tuj1 and NEFH) and the oligodendrocyte marker (CNP) was significantly increased with MS-275 or VPA treatment compared to that with RA treatment. In addition, the protein expression of the other neuronal markers, Tuj1 and NeuN, was highly increased with HDAC inhibitor treatments compared to that with RA treatment. Furthermore, we confirmed that noncanonical Wnt signaling was upregulated by HDAC inhibitors via MAPK signaling and the Wnt/JNK pathway. Therefore, both MS-275 and VPA promoted the differentiation of SH-SY5Y cells into mature neurons via the Wnt signaling pathway.

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“…Previously, HDAC1 and HDAC2 silencing and overexpression were reported to regulate osteogenesis in cell types other than MSCs; however, one has a positive effect 48,49 which means they enhance osteogenesis, whereas the other shows negative effects 47,50 which means they regulate the expression of the osteogenic gene osteocalcin or the osteoclastogenic gene RANKL. Therefore, these results should be considered characteristic effects of hBM‐MSCs interacting with periodontal cells, HPL cells, and HGFs, and studied further.…”

Section: Discussionmentioning

confidence: 99%

Regulation of osteogenesis in bone marrow‐derived mesenchymal stem cells via histone deacetylase 1 and 2 co‐cultured with human gingival fibroblasts and periodontal ligament cells

Iwata

Kaneda‐Ikeda

Takahashi

et al. 2022

J of Periodontal Research

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Objective This study aimed to determine the regulatory mechanism of bone marrow‐derived mesenchymal stem cell (BM‐MSC) differentiation mediated by humoral factors derived from human periodontal ligament (HPL) cells and human gingival fibroblasts (HGFs). We analyzed histone deacetylase (HDAC) expression and activity involved in BM‐MSC differentiation and determined their regulatory effects in co‐cultures of BM‐MSCs with HPL cells or HGFs. Background BM‐MSCs can differentiate into various cell types and can, thus, be used in periodontal regenerative therapy. However, the mechanism underlying their differentiation remains unclear. Transplanted BM‐MSCs are affected by periodontal cells via direct contact or secretion of humoral factors. Therefore, their activity is regulated by humoral factors derived from HPL cells or HGFs. Methods BM‐MSCs were indirectly co‐cultured with HPL cells or HGFs under osteogenic or growth conditions and then analyzed for osteogenesis, HDAC1 and HDAC2 expression and activity, and histone H3 acetylation. BM‐MSCs were treated with trichostatin A, or their HDAC1 or HDAC2 expression was silenced or overexpressed during osteogenesis. Subsequently, they were evaluated for osteogenesis or the effects of HDAC activity. Results BM‐MSCs co‐cultured with HPL cells or HGFs showed suppressed osteogenesis, HDAC1 and HDAC2 expression, and HDAC phosphorylation; however, histone H3 acetylation was enhanced. Trichostatin A treatment remarkably suppressed osteogenesis, decreasing HDAC expression and enhancing histone H3 acetylation. HDAC1 and HDAC2 silencing negatively regulated osteogenesis in BM‐MSCs to the same extent as that achieved by indirect co‐culture with HPL cells or HGFs. Conversely, their overexpression positively regulated osteogenesis in BM‐MSCs. Conclusion The suppressive effects of HPL cells and HGFs on BM‐MSC osteogenesis were regulated by HDAC expression and histone H3 acetylation to a greater extent than that mediated by HDAC activity. Therefore, regulation of HDAC expression has prospects in clinical applications for effective periodontal regeneration, mainly, bone regeneration.

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Valproic Acid-Induced CCN1 Promotes Osteogenic Differentiation by Increasing CCN1 Protein Stability through HDAC1 Inhibition in Tonsil-Derived Mesenchymal Stem Cells

Cited by 15 publications

References 47 publications

Molecular data representation based on gene embeddings for cancer drug response prediction

Molecular data representation based on gene embeddings for cancer drug response prediction

Effects of HDAC inhibitors on neuroblastoma SH-SY5Y cell differentiation into mature neurons via the Wnt signaling pathway

Regulation of osteogenesis in bone marrow‐derived mesenchymal stem cells via histone deacetylase 1 and 2 co‐cultured with human gingival fibroblasts and periodontal ligament cells

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