HDGFR2 regulates osteogenic differentiation by balancing histone crotonoylation and acetylation modifications [Cut & Tag]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE263961 | GEO | 2024/04/19
REPOSITORIES: GEO
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Project description:Epigenetics regulates the expression of osteogenic genes and mediates the osteogenic differentiation of MSCs. It was found that hepatoma-derived growth factor (HDGFR2) is a histone methylated reader protein, which can recognize histone methylation modification and play an important "switch" role in gene transcriptional regulation. It is unclear whether HDGFR2 is involved in bone formation studies. Our study aims to investigate the effect of HDGFR2 on osteogenic differentiation and provide evidence for BMSCs as seed cells for tissue regeneration. We found that compared with the wild-type (WT) mice, the bone mass of the femur and the root furcation bone in HDGFR2-KO mice was significantly elevated to attenuate age-related bone loss. Compared with the BMSCs in WT mice, the cloning and osteogenic differentiation of BMSCs in HDGFR2-KO mice were significantly accelerated, and vice versa when HDGFR2 was overexpressed. GO analysis suggested that differential genes were mainly involved in osteoblast differentiation, ossification, collagen fiber tissue and mineralization. The bone defect repair ability of HDGFR2-KO mice was significantly enhanced compared to the control group. Moreover, the depletion of HDGFR2 suppressed periodontal bone loss. The HDGFR2 interacts with the active regulator of SIRT1 (AROS) and sirtuin family deacetylases to form a chromatin remodeling complex, and AROS regulated osteogenesis through combining with HDFGR2. The decreased ratio of H3K18 crotonylation to acetylation improved the transcription of osteogenic genes in HDGFR2 knockout BMSCs. Taken together, these data demonstrated that the knockdown of HDGFR2 could promote osteogenic differentiation and bone repair, providing a new theoretical basis for bone tissue regeneration.
2024-04-19 | GSE263962 | GEO
Project description:Pathological processes like osteoporosis or steroid-induced osteonecrosis of the hip are accompanied by increased bone marrow adipogenesis. Such disorder of adipogenic/osteogenic differentiation, which affects also bone marrow derived mesenchymal stem cells (BMSCs) contributes to bone loss during aging. Therefore, we investigated the effects of extracellular vesicles (EVs) isolated from human (h)BMSCs during different stages of osteogenic differentiation on osteogenic and adipogenic differentiation capacity of naïve hBMSCs.
2022-10-14 | PXD035845 | Pride
Project description:Background: Dicalcium cilicate (C2S) is a potent biomaterial for bone regeneration application. Circular RNA (circRNAs) plays crucial role in osteogenic differentiation of mesenchymal stem cells (MSCs) and bone defect healing. In this study, we aim to elucidate the differential expression of circ_RNAs and mRNAs in C2S-treated MSCs, the role of circ_1983 in C2S-mediated bone regeneration, and its mechanism. Methods: The effect of C2S on osteogenic differentiation of mice bone marrow-derived MSCs (BMSCs) and rat cranial bone defect healing were analyzed. Differential expression of circ-RNAs and mRNAs in C2S-treated BMSCs were profiled by RNA-sequencing. The interaction between circ_1983 and miR-6931 was confirmed by pull-down and dual luciferase reporter assays. ceRNA function of circ_1983 via sponging miR-6931 and targeting Gas7 mRNA expression in BMSCs was analyzed by miRanda (http://www.microrna.org/microrna/). Role of circ_1983 in C2S-induced osteogenic differentiation of BMSCs was analyzed by shRNA-mediated knockdown of circ_1983. Results: C2S enhanced osteogenic differentiation of BMSCs and bone defect healing. CircRNAs (total 1384) and mRNAs (total 1725) were differentially upregulated in C2S-treated BMSCs. Upregulated circRNAs and ceRNA-interaction networks were associated with osteogenesis-related signaling pathways, i.e. MAPK, PI3K-Akt. RNA-sequencing and qRT-PCR results confirmed upregulation of circ_1983 in C2S-tretaed BMSCs. Circ_1983 showed ceRNA effect by sponging miR-6931 and overexpressing Gas mRNA that enhanced Runx2 expression and promoted osteogenic differentiation of BMSCs. Knockdown of circ_1983 inhibited the C2S-induced osteogenic differentiation of BMSCs. Interpretation: C2S-induced circ_1983 upregulation in BMSCs sponges miR-6931 and targets Gas7 gene to enhance Runx2 expression thereby promotes osteogenic differentiation and bone regeneration.
2021-04-12 | GSE140273 | GEO
Project description:The treatment of bone defects caused by infection, trauma or neoplasms remains a clinical challenge. Autologous bone transplantation is limited by availability, donor site morbidity and surgical risk factors. This has given rise to stromal/stem-cell based therapy. Bone marrow derived stromal cells (BMSCs) have been studied to a large extent and show high regenerative potential but their use is limited by availability, donor site morbidity and the relatively low cell yield as they represent only <0.1% of cell harvested from bone marrow aspirate. At the same time, they are the closest mesenchymal stromal cells for bone tissue engineering given their tissue origin and, unlike other mesenchymal stromal cells, can support the formation of hematopoietic marrow. Adipose tissue derived stromal cells (ASCs) as part of the stromal vascular fraction of adipose tissue can as well undergo osteogenic differentiation but can be additionally isolated in a sufficient quantity from lipoaspirate after liposuction of abundant subcutaneous fat tissue. Here, it has been shown that there are no major differences in regard to proliferation or differentiation capacity of ASCs derived from subcutaneous fat of different anatomical regions. It has been shown that BMSCs are more prone to senescence during expansion and passage than ASCs and that ageing impacts proliferative capabilities of BMSCs more than that of ASCs while it has also been reported that osteogenic differentiation capacity is least impacted by age. Multiple studies have compared the characteristics of these two mesenchymal stromal cells in regard to bone tissue engineering in vitro. Most studies point to inferior extracellular matrix mineralization and lower expression of key osteogenic transcription markers like Runx2 in osteogenic differentiated ASCs compared to BMSCs. On the other hand, a study by Rath et al. found contrary results using particular culturing conditions like 3D bioglass scaffolds. An intraindividual comparison of human MSCs of three donors cultured on decellularized porcine bone confirmed superior osteogenic capacity of BMSCs compared to ASCs. In contrast to BMSCs, ASCs were not able to induce heterogenic ossification in a mouse model. In a sheep tibia defect model application of BMSCs resulted in a significantly higher amount of newly formed bone tissue. Importantly, Osteogenic differentiated ASCs do not support the formation of a hematopoietic marrow. Proteomics enables large-scale analysis of proteins present in a cell type and can be used to identify differentially regulated key proteins in a comparative approach. A comparative proteomic analysis of BMSCs and ASCs by Roche et al. in 2009 identified 556 proteins with 78% of these not being differentially regulated between these two cell populations, regarded as high similarity. Another comparative proteomic study of 2016 by Jeon et al. found 90 differentially regulated proteins out of 3000 total identified proteins. Both studies do not specify a number of different tissue donors and in part using cell lines. Looking for differences upon osteogenic differentiation, transcriptomic comparison of osteogenic differentiated porcine ASCs and BMSCs has been performed, resulting in 21 differentially expressed genes after 21 days of osteogenic culture conditions. Still, it remains unanswered, which are the key distinctive features of osteogenic differentiated ASCs and BMSCs at protein level that might help address the abovementioned weaknesses of ASCs in bone tissue engineering/regeneration for translational research. To overcome this need, an intraindividual comparative DIA based proteomic analysis of osteogenic differentiated human BMSC and ASCs was performed in this study.
2021-06-09 | PXD015223 | Pride
Project description:To further reveal key mRNAs deciding osteogenic, adipogenic, and chondrogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in early phases, we have employed next-generation high-throughput transcriptome sequencing to detect the expression of mRNA in rat BMSCs during differentiation.
2021-10-23 | GSE185140 | GEO
Project description:Osteogenesis is a complex process of bone formation regulated by various factors, yet its underlying molecular mechanisms remain incompletely understood. This study aimed to investigate the role of S100A16, a novel member of the S100 protein family, in the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) and uncover a novel Smad4-mitogen-activated protein kinase (MAPK)/Jun N-terminal kinase (JNK) signaling axis. We herein evaluated the expression level of S100A16 in bone tissues and BMSCs from ovariectomized rats and then examined the impact of S100A16 silencing on osteogenic differentiation. Increased S100A16 expression was observed in bone tissues and BMSCs from ovariectomized rats, and S100A16 silencing promoted osteogenic differentiation. Further transcriptomic sequencing revealed that the Smad4 pathway was involved in S100A16 silencing-induced osteogenesis. The results of our Western blot analysis showed that S100A16 overexpression not only downregulated Smad4 but also activated MAPK/JNK signaling, which was validated by treatment with MAPK and JNK inhibitors U0126 and SP600125. Overall, this study elucidated the novel regulatory factors influencing osteogenic differentiation and provided mechanistic insights that could aid in the development of targeted therapeutic strategies for osteoporosis patients.
2024-03-08 | GSE259238 | GEO
Project description:Melatonin (MT) has been proposed as a treatment for OP, but the therapeutic effect of this agent needs further validation and the mechanisms remain to be explored. In this study, we observed that MT markedly stimulated osteogenic differentiation of BMSCs, and alleviated OP symptoms in mice. To explore the molecular mechanism of MT regulating differentiation of BMSCs, the proteomics analyses were conducted, and the multiple important genes were found. Importantly, it was found that MT could promote expression of thioredoxin1 (TRX1) in vivo and in vitro conditions, while its expression notably decreased in osteoporotic mice, thereby suggesting this gene might mediate the therapeutic effect of MT on OP. Moreover, the following overexpression or silencing of TRX1 proved its ability to induce osteogenesis of BMSCs. Furthermore, osteogenic differentiation and OP after MT pretreatment was attenuated both in BMSCs and in mice with Trx1 knockdown. These findings confirm that TRX1 is potentially associated with the beneficial effects of MT and that the use of MT may reduce OP.
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Project description:Chromodomain helicase DNA-binding protein 7 (CHD7) is an ATP-dependent chromatin remodeling enzyme, functioning as chromatin reader to conduct epigenetic modification. Its effect on osteogenic differentiation of human dental follicle cells (hDFCs) remains unclear. Here we show CHD7 expression increases with osteogenic differentiation. knockdown of CHD7 impairs the osteogenic ability of hDFCs, characterized by reduced alkaline phosphatase activity and mineralization, and decreased expression of osteogenesis-related genes. Conversely, CHD7 overexpression enhances the osteogenic differentiation of hDFCs. Mechanically, RNA-seq analyses revealed the down-regulated enrichment of PTH (parathyroid hormone)/PTH1R (parathyroid hormone receptor-1) signaling pathway after CHD7 knockdown. We found the expression of PTH1R positively correlates with CHD7. Importantly, overexpression of PTH1R in CHD7-knockdown hDFCs partially rescued the impaired osteogenic differentiation. Our research demonstrates that CHD7 regulates the osteogenic differentiation of hDFCs by regulating the transcription of PTH1R.
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Project description:Changes in these genes are probably a consequence of aging, and the real regulators governing BMSC senescence and osteogenesis are still unclear.In the current study, we report that nucleosome assembly-related protein NAP1L2 serves as an important regulator of both the senescence and osteogenic differentiation of BMSCs through inhibition of NF-κB signaling and recruitment of SIRT1 to deacetylate the H3K14ac level on promoters of osteogenic genes. Thus, targeting NAP1L2 using an aging antagonist such as NMN would benefit aging-related disease.
2021-02-06 | GSE166243 | GEO
Project description:Changes in these genes are probably a consequence of aging, and the real regulators governing BMSC senescence and osteogenesis are still unclear.In the current study, we report that nucleosome assembly-related protein NAP1L2 serves as an important regulator of both the senescence and osteogenic differentiation of BMSCs through inhibition of NF-κB signaling and recruitment of SIRT1 to deacetylate the H3K14ac level on promoters of osteogenic genes. Thus, targeting NAP1L2 using an aging antagonist such as NMN would benefit aging-related disease.
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