Hypermethylation in Calca Promoter Inhibited ASC Osteogenic Differentiation in Rats with Type 2 Diabetic Mellitus

Wang, Lei; Ding, Feng; Shi, Shaojie; Wang, Xingxing; Zhang, Sijia; Song, Yingliang

doi:10.1155/2020/5245294

Cited by 4 publications

(6 citation statements)

References 36 publications

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“…ADSCs were isolated from groin fat of young rats as previously described [ 43 ]. Adherent cells were cultured in a α-MEM medium with 10% FBS and 1% penicillin–streptomycin.…”

Section: Methodsmentioning

confidence: 99%

TRAF6 promotes osteogenesis in ADSCs through Raf-Erk-Merk-Hif1-a pathway

et al. 2023

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Critical-size defects (CSDs) are challenging oral clinical issues that need to be solved. Adipose-derived mesenchymal stem cells (ADSCs) and gene therapy offer a new target to solve these issues. Consequently, ADSCs attract more and more attention because of advantages such as easy obtainability and no ethical concerns. TNF receptor-associated factor 6 (TRAF6) is a significant binding protein both of tumour necrosis factor superfamily and of the toll/interleukin-1 receptor superfamily. Evidence is accumulating that TRAF6 inhibited osteoclast formation and promoted the proliferation of multiple myeloma cell lines and bone resorption. Here, we reported that overexpression of TRAF6 enhanced the proliferation, migration and osteogenesis of ADSCs through Raf-Erk-Merk-Hif1a pathway. Cell sheet of ADSCs combined with TRAF6 accelerated the healing of CSDs. In a word, TRAF6 enhanced osteogenesis, migration and proliferation through Raf-Erk-Merk-Hif1a pathway.

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“…ADSCs were isolated from groin fat of young rats as previously described [ 43 ]. Adherent cells were cultured in a α-MEM medium with 10% FBS and 1% penicillin–streptomycin.…”

Section: Methodsmentioning

confidence: 99%

TRAF6 promotes osteogenesis in ADSCs through Raf-Erk-Merk-Hif1-a pathway

et al. 2023

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“…Studies showed that adipose-derived stem cells (ASCs) in patients with type 2 diabetes mellitus (T2DM) caused upregulation of methylation level in promoter region of CALCA target fragment, resulting in a significant reduction in the osteogenic function of stem cells [ 35 ]. The above studies indicated that the abnormal methylation level of CALCA segments in stem cells may change the cell stemness on bone stem cells.…”

Section: Cgrp and Bone Stem Cellsmentioning

confidence: 99%

“…CpG island hypermethylation of CALCA occurs in juvenile mononuclear leukemia (JMML), regaining the hypermethylated phenotype upon relapse after treatment [ 161 ]. Thus, the abnormal methylation level of CALCA fragment in the promoter region of stem cells is an important reason for the change of cell stemness [ 35 ], and high-methylation phenotype is also an important biomarker in the process of tumor diagnosis and treatment.…”

Section: Cgrp and Tumor Stem Cellsmentioning

confidence: 99%

“…Cytosine residue methylation is the most widely studied epigenetic modification, which mostly exists in CG sequence [ 34 ]. Different elements such as promoter, gene ontology, enhancer, silencer, and transposon in genome can be methylated and affect gene expression [ 35 ]. About half of the genes in vertebrates are enriched in CpG sequences on the promoter, which is called CpG island.…”

Section: Introductionmentioning

confidence: 99%

“…DNA methylation regulates cell proliferation, apoptosis, and gene expression, which is closely related to tumor [ 33 , 39 ]. Abnormal methylation levels of CALCA promoter and exon can change cell stemness [ 35 , 40 ]. Methylation of CALCA promoter in bone marrow cells is often observed in patients with myelodysplastic syndrome (MDS) so demethylated drugs can delay the progression of MDS [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

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CGRP: A New Endogenous Cell Stemness Maintenance Molecule

Chen

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Stem cells have the ability of self-replication and multidirectional differentiation, but the mechanism of how stem cells “maintain” this ability and how to “decide” to give up this state and differentiate into cells with specific functions is still unknown. The Nobel Prize in physiology and medicine in 2021 was awarded to “temperature and tactile receptor,” which made the pain receptor TRPV1-calcitonin gene-related peptide (CGRP) pathway active again. The activation and blocking technology of CGRP has been applied to many clinical diseases. CGRP gene has complex structure and transcription process, with multiple methylation and other modification sites. It has been considered as a research hotspot and difficulty since its discovery. Drug manipulation of TRPV1 and inhibition of CGRP might improve metabolism and prolong longevity. However, whether the TRPV1-neuropeptide-CGRP pathway is directly or indirectly involved in stem cell self-replication and multidirectional differentiation is unclear. Recent studies have found that CGRP is closely related to the migration and differentiation of tumor stem cells, which may be realized by turning off or turning on the CGRP gene expression in stem cells and activating a variety of ways to regulate stem cell niches. In this study, we reviewed the advances in researches concentrated on the biological effects of CGRP as a new endogenous switching of cell stemness.

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