Genetics and Epigenetics of Bone Remodeling and Metabolic Bone Diseases

Otòn-Gonzalez, Lucia; Mazziotta, Chiara; Iaquinta, Maria Rosa; Mazzoni, Elisa; Nocini, Riccardo; Trevisiol, Lorenzo; D’Agostino, Antonio; Tognon, Mauro; Rotondo, John Charles; Martini, Fernanda

doi:10.3390/ijms23031500

Cited by 37 publications

(30 citation statements)

References 203 publications

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“…The methylation status determines the propensity of bone marrow-derived MSCs to differentiate towards osteoblasts, which may be associated with hypomethylation of the promoter regions of the osteogenic genes RUNX2 and OCN, and higher expression of the corresponding mRNAs. In addition, methylation regulation of the Wnt/b-catenin signalling pathway and the RANKL/RANK/ OPG system also plays an important role in bone regeneration (Oton-Gonzalez et al, 2022). The studies related to DNA methylation in periapical inflammation are currently inadequate, and the elucidation of the relevant mechanisms depends on further studies.…”

Section: Dna Methylationmentioning

confidence: 99%

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Xu-tao

Wan

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

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Chronic periapical periodontitis (CAP) is a typical oral disease in which periodontal inflammation caused by an odontogenic infection eventually leads to bone loss. Uncontrolled infections often lead to extensive bone loss around the root tip, which ultimately leads to tooth loss. The main clinical issue in the treatment of periapical periodontitis is the repair of jawbone defects, and infection control is the first priority. However, the oral cavity is an open environment, and the distribution of microorganisms through the mouth in jawbone defects is inevitable. The subversion of host cell metabolism by oral microorganisms initiates disease. The presence of microorganisms stimulates a series of immune responses, which in turn stimulates bone healing. Given the above background, we intended to examine the paradoxes and connections between microorganisms and jaw defect repair in anticipation of new ideas for jaw defect repair. To this end, we reviewed the microbial factors, human signaling pathways, immune cells, and cytokines involved in the development of CAP, as well as concentrated growth factor (CGF) and stem cells in bone defect repair, with the aim of understanding the impact of microbial factors on host cell metabolism to inform the etiology and clinical management of CAP.

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Section: Dna Methylationmentioning

confidence: 99%

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Xu-tao

Wan

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

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“…It regulates the T and B immune response through the TGFB1: CXCR4 interaction ( 35 ). It mediates osteoclast activation in bone remodeling and tumor angiogenesis ( 36 , 37 ). Together, we noticed that C14 and C25 acted as a bridge between tumor components and nontumor components.…”

Section: Resultsmentioning

confidence: 99%

Development of a Chemoresistant Risk Scoring Model for Prechemotherapy Osteosarcoma Using Single-Cell Sequencing

Zeng

Zhang

et al. 2022

Front. Oncol.

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BackgroundChemoresistance is one of the leading causes that severely limits the success of osteosarcoma treatment. Evaluating chemoresistance before chemotherapy poses a new challenge for researchers. We established an effective chemoresistance risk scoring model for prechemotherapy osteosarcoma using single-cell sequencing.MethodsWe comprehensively analyzed osteosarcoma data from the bulk mRNA sequencing dataset TARGET-OS and the single-cell RNA sequencing (scRNA-seq) dataset GSE162454. Chemoresistant tumor clusters were identified using enrichment analysis and AUCell scoring. Its differentiated trajectory was achieved with inferCNV and pseudotime analysis. Ligand–receptor interactions were annotated with iTALK. Furthermore, we established a chemoresistance risk scoring model using LASSO regression based on scRNA-seq-based markers of chemoresistant tumor clusters. The TARGET-OS dataset was used as the training group, and the bulk mRNA array dataset GSE33382 was used as the validation group. Finally, the performance was verified for its discriminatory ability and calibration.ResultsUsing bulk RNA data, we found that osteogenic expression was upregulated in chemoresistant osteosarcoma as compared to chemosensitive osteosarcoma. Then, we transferred the bulk RNA findings to scRNA-seq and noticed osteosarcoma tumor clusters C14 and C25 showing osteogenic cancer stem cell expression patterns, which fit chemoresistant characteristics. C14 and C25 possessed bridge roles in interactions with other clusters. On the one hand, they received various growth factor stimulators and could potentially transform into a proliferative state. On the other hand, they promote local tumor angiogenesis, bone remodeling and immunosuppression. Next, we identified a ten-gene signature from the C14 and C25 markers and constructed a chemoresistant risk scoring model using LASSO regression model. Finally, we found that chemoresistant osteosarcoma had higher chemoresistance risk score and that the model showed good discriminatory ability and calibration in both the training and validation groups (AUCtrain = 0.82; AUCvalid = 0.84). Compared with that of the classic bulk RNA-based model, it showed more robust performance in validation environment (AUCvalid-scRNA = 0.84; AUCvalid-bulk DEGs = 0.54).ConclusionsOur work provides insights into understanding chemoresistant osteosarcoma tumor cells and using single-cell sequencing to establish a chemoresistance risk scoring model. The model showed good discriminatory ability and calibration and provided us with a feasible way to evaluate chemoresistance in prechemotherapy osteosarcoma.

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“…Furthermore, it has been acknowledged that the tendency of MSCs from different origin towards certain cell fate is also dictated by the 12 Stem Cells International DNA methylation status. For example, hypomethylation of osteogenic genes was found in BM-MSCs, but in AD-MSCs, adipogenic genes were hypomethylated instead [72]. Yang et al [73] demonstrated that DNMT1 promoted adipogenesis at early stage but not inhibiting this process at late stage, suggesting DNMT1 governed adipogenic commitment in a time-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Collagen Modulates the Biological Characteristics of WJ-MSCs in Basal and Osteoinduced Conditions

Hiew

Teoh

2022

Stem Cells International

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Transcriptomic analysis revealed mesenchymal stem/stromal cells (MSCs) from various origins exhibited distinct gene and protein expression profiles dictating their biological properties. Although collagen type 1 (COL) has been widely studied in bone marrow MSCs, its role in regulating cell fate of Wharton jelly- (WJ-) MSCs is not well understood. In this study, we investigated the effects of collagen on the characteristics of WJ-MSCs associated with proliferation, surface markers, adhesion, migration, self-renewal, and differentiation capabilities through gene expression studies. The isolated WJ-MSCs expressed positive surface markers but not negative markers. Gene expression profiles showed that COL not only maintained the pluripotency, self-renewal, and immunophenotype of WJ-MSCs but also primed cells toward lineage differentiations by upregulating BMP2 and TGFB1 genes. Upon osteoinduction, WJ-MSC-COL underwent osteogenesis by switching on the transcription of BMP6/7 and TGFB3 followed by activation of downstream target genes such as INS, IGF1, RUNX2, and VEGFR2 through p38 signalling. This molecular event was also accompanied by hypomethylation at the OCT4 promoter and increase of H3K9 acetylation. In conclusion, COL provides a conducive cellular environment in priming WJ-MSCs that undergo a lineage specification upon receiving an appropriate signal from extrinsic factor. These findings would contribute to better control of fate determination of MSCs for therapeutic applications related to bone disease.

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Genetics and Epigenetics of Bone Remodeling and Metabolic Bone Diseases

Cited by 37 publications

References 203 publications

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Development of a Chemoresistant Risk Scoring Model for Prechemotherapy Osteosarcoma Using Single-Cell Sequencing

Collagen Modulates the Biological Characteristics of WJ-MSCs in Basal and Osteoinduced Conditions

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