Chaetocin Promotes Osteogenic Differentiation via Modulating Wnt/Beta-Catenin Signaling in Mesenchymal Stem Cells

Liang, Youde; Liu, Xin; Zhou, Ruiping; Song, Dawei; Jiang, Yi‐Zhou; Xue, Weiwei

doi:10.1155/2021/8888416

Cited by 14 publications

(15 citation statements)

References 20 publications

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“…Suppression of EZH2 prevents BMSCs from differentiating into adipocytes rather than osteoblasts, resulting in increased bone formation during OP [ 42 ]. Knockdown of SUV39H1, a methyltransferase of H3K9me3, or its auxiliary factor HP1α will down-regulate H3K9me3 and lead to BMSC senescence, while overexpression of HP1α would up-regulate H3K9me3 level, thus promoting BMSC osteogenic differentiation [ 41 ]. The regulation modes of histone modification enzymes (summarized in Table 2 ) can provide viewpoints for further exploration.…”

Section: Treating Target For Histone Modificationmentioning

confidence: 99%

“…Both G9a and SUV39h1/2 could catalyze the methylation of H3K9, but the same inhibitory histone modification H3K9me3 produces different results. G9a inhibitors (e.g., A366, BIX01294) promote adipogenesis [ 37 ], but SUV39h1/2 inhibitors (e.g., chaetocin) promote osteogenesis [ 41 ]. In conclusion, different inhibitors exert different effects, which is critical and calls for researchers’ attention in selecting inhibitors.…”

Section: Treating Target For Histone Modificationmentioning

confidence: 99%

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Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases

Zhao

Qiu

et al. 2022

Stem Cell Res Ther

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As global aging accelerates, the prevention and treatment of age-related bone diseases are becoming a critical issue. In the process of senescence, bone marrow mesenchymal stem cells (BMSCs) gradually lose the capability of self-renewal and functional differentiation, resulting in impairment of bone tissue regeneration and disorder of bone tissue homeostasis. Alteration in epigenetic modification is an essential factor of BMSC dysfunction during aging. Its transferability and reversibility provide the possibility to combat BMSC aging by reversing age-related modifications. Emerging evidence demonstrates that epigenetic therapy based on aberrant epigenetic modifications could alleviate the senescence and dysfunction of stem cells. This review summarizes potential therapeutic targets for BMSC aging, introduces some potential approaches to alleviating BMSC aging, and analyzes its prospect in the clinical application of age-related bone diseases.

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Section: Treating Target For Histone Modificationmentioning

confidence: 99%

Section: Treating Target For Histone Modificationmentioning

confidence: 99%

Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases

Zhao

Qiu

et al. 2022

Stem Cell Res Ther

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“…Recent studies have shown that Wnt/β-catenin signaling plays an important role in the osteogenic differentiation of MSCs ( Li et al, 2019 ; Liang et al, 2021 ). To explore whether Gli1+ progenitors are regulated by Wnt/β-catenin signaling, we harvested tdTomato + cells from Gli1-Cre ERT2 ;tdTomato condyles 1 week after induction.…”

Section: Resultsmentioning

confidence: 99%

Gli1+ Osteogenic Progenitors Contribute to Condylar Development and Fracture Repair

Chen

Lan

Lei

et al. 2022

Front. Cell Dev. Biol.

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The condyle plays a pivotal role in mandible development, which is regulated by various signaling molecules. The hedgehog (Hh) signaling pathway is known to modulate several processes during bone formation. However, the role of Gli1, as the read-out of Hh signaling activity, in condylar development and fracture healing has not been clarified. In this study, we discovered that a population of Gli1+ cells residing immediately below the cartilage functions as osteogenic progenitors by using Gli1-CreERT2;tdTomato mice. These Gli1+ cells contributed to nearly all osteoblasts in the subchondral bone during condyle postnatal development. Interestingly, Gli1-lineage cells could differentiate into osteoblasts and chondrocytes during fracture healing. Inhibiting Wnt/β-catenin signaling downregulated the proliferation and differentiation of Gli1+ cells in vitro. These findings suggest that Gli1+ progenitor cells participate in not only normal bone formation but also fracture healing; moreover, these cells may provide a potential target for promoting bone regeneration of the mandible.

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“…When DNA methylation was modulated in vitro in osteogenic progenitors, it was demonstrated that DNA methyltransferase 1 (DNMT1) inhibition in periodontal ligament cells restored RUNX2 expression and their osteogenic capacity, and inhibition of methylation in MSC supported osteogenic differentiation at the cost of adipogenic capacity. For KDM7A, a role in a reciprocal mechanism for the switch between osteogenic and adipogenic differentiation was also reported [44,57,58]. On the other hand, osteogenic receptors like PTH1R or the vitamin D receptor VDR may, vice versa, modulate the expression of epigenetically relevant components [59,60].…”

Section: Alu Elements Highmentioning

confidence: 86%

Epigenetics of Osteoporosis

et al. 2021

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Fragile bone is the root cause of osteoporosis. For inherited or acquired reasons, the fragile bone does not provide sufficient fracture resistance to withstand the physical strains of a normal lifestyle. Accordingly, clinical characteristics consist of fragility fractures that occur during daily life activities or low energy trauma. Hip fractures and vertebral fractures are so called "major osteoporotic fractures”, that also cause the highest burden of disease. Although the clinical osteoporosis manifestations are relatively uniform, there is a vast spectrum of underlying molecular causes. Impaired bone formation, accelerated bone loss, and impaired lifetime adaptive regeneration according to physical impact characterize the cruder facets of osteoporosis. The signaling cascades that govern bone formation and metabolism may be altered by genetically or epigenetically inherited defects or acquired epigenetic changes due to tissue aging and/or underlying diseases. While molecular genetics and mechanisms and specific osteoporosis treatments have made impressive progress over the last three decades, there is still an urgent need to better understand the role of epigenetics in this disease.Epigenetic mechanisms such as covalent modifications of DNA, histones, or essential core factors like the osteogenic transcription factors (e. g., RUNX2) and inhibitory modulators of osteogenic WNT-signaling (e. g., Dickkopf-1 (DKK-1), sclerostin (SOST)) are all intricately implicated in developmental bone formation and adaptive regeneration and remodeling processes throughout adult life. These mechanisms are accompanied by chromatin architecture and gene expression changes of small (e. g., microRNAs (miRs)) and long, noncoding RNAs (lncRNAs). The timely execution of these mechanisms either facilitates or inhibits bone formation and remodeling. Together, epigenetic mechanisms controlling bone homeostasis widen the spectrum of potential dysregulations that can cause osteoporosis and open new avenues for therapeutic interventions.Apart from the core mechanisms of bone formation and regeneration, recent research revealed that tissue-resident cells of the immune system such as tissue-specific macrophages, myeloid precursors, and lymphocytes have surprisingly fundamental influence on tissue regeneration, including bone. Those tissue resident cells are also subject to epigenetic changes and may substantially contribute to the development of disease. Epigenetic constellations can be inherited, but the dynamic epigenetic mechanisms involved in physiological processes of tissue regeneration may also be affected by pathologies such as cellular aging and senescence. Recently, several studies aimed at identifying DNA methylation signatures in peripheral blood leukocytes from osteoporosis patients that reveal novel disease mechanisms and potential targets for diagnosis and treatment. Overall, these studies rendered, however, yet inconclusive results.By contrast, studies using bone marrow-derived skeletal progenitors identified transcriptome changes in osteoporosis patients, which could have epigenetic reasons in the absence of genetic causes. Respective changes may be related to the local milieu in bone and bone marrow as a kind of segmental attitude of a specific tissue acquired through tissue aging and/or supported by underlying aging-associated diseases such as arteriosclerosis or aging of cells of the immune system.In summary, there is cumulating evidence linking epigenetic factors to the pathogenesis of aging-associated osteoporosis. However, we are currently still limited in our knowledge with respect to the causal traits that are common, inherited, or acquired in a lifetime in the respective tissues and cells involved in bone formation and regeneration. During the following years, the field will most certainly learn more about molecular processes and factors that can be targeted therapeutically and/or used as biomarkers for risk assessment.

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Chaetocin Promotes Osteogenic Differentiation via Modulating Wnt/Beta-Catenin Signaling in Mesenchymal Stem Cells

Cited by 14 publications

References 20 publications

Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases

Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases

Gli1+ Osteogenic Progenitors Contribute to Condylar Development and Fracture Repair

Epigenetics of Osteoporosis

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