Epigenetic regulation of bone cells

Park-Min, Kyung Hyun

doi:10.1080/03008207.2016.1177037

Cited by 30 publications

(24 citation statements)

References 157 publications

(145 reference statements)

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“…However, we observed that lycopene significantly repressed the expression level of DNMT3a but did not affect DNMT1 and DNMT3b. Previous studies have demonstrated that DNMT3a is a negative regulator of IRF8 [31]. Therefore, this result further indicates that lycopene treatment affecting the mRNA levels of IRF1 and IRF7 may only be caused by its role in IFNγ.…”

Section: Discussionsupporting

confidence: 57%

Lycopene improves the efficiency of anti-PD-1 therapy via activating IFN signaling of lung cancer cells

Jiang¹,

Wu²,

Zhao³

et al. 2019

Cancer Cell Int

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BackgroundMonoclonal antibodies targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) have been developed to treat cancers including lung cancer. In this study, we aimed to investigate whether lycopene could promote the effect of anti-PD-1 treatment on lung cancer.MethodsTumor formation assay was conducted. Immune reactions were assessed by detecting several cytokine levels using enzyme-like immunosorbent assay. T cell activity was analyzed using cytometry. The mechanism of lycopene action was investigated using Western blot, quantitative real-time polymerase chain reaction and bisulfite sequencing analysis.ResultsAfter the mice injected with Lewis lung carcinoma (LLC) cells were sacrificed, we found that combined lycopene and anti-PD-1 reduced the tumor volume and weight compared to control treatment. Cell apoptosis in the tumor tissues was significantly enhanced in mice with combined lycopene and anti-PD-1 treatment in comparison with those of either lycopene or anti-PD-1 alone. Furthermore, lycopene could assist anti-PD-1 to elevate the levels of interleukin (IL)-1 and interferon (IFN) γ while reduce the levels of IL-4 and IL-10 in the spleen of mice injected with LLC cells. Lycopene treatment increased the CD4+/CD8+ ratio in the spleen and promoted IFNγ-expressing CD8+ T cells in tumor tissues. Upon IFNγ stimulation, lycopene diminished PD-L1 expression via activating JAK and repressing phosphorylation of AKT.ConclusionOur results have demonstrated that lycopene could be used as a potential adjuvant drug to synergistically improve the efficiency of anti-PD-1 therapy.Electronic supplementary materialThe online version of this article (10.1186/s12935-019-0789-y) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 57%

Lycopene improves the efficiency of anti-PD-1 therapy via activating IFN signaling of lung cancer cells

Jiang¹,

Wu²,

Zhao³

et al. 2019

Cancer Cell Int

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“…Chromatin condensation and histone acetylation are regulated by epigenetic modulators, such as type I HDACs. HDAC1, HDAC2, and HDAC3 have been implicated in playing a role in osteogenic differentiation of hMSCs ( 20 , 29 – 31 ). To investigate whether disruption of the KASH domain leads to altered activity and levels of HDAC enzymes, we analyzed mRNA expression of HDAC1, HDAC2, and HDAC3.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that epigenetic remodeling is important in precise regulation of gene expression of hMSCs in bone development and remodeling ( 13 , 18 , 19 ). It has been suggested that perturbation of epigenetic programs, leading to changes in histone acetylation landscapes and chromatin structure, can affect the function and activity of hMSCs and contributes to pathologies defined by bone loss (osteoporosis, osteoarthritis) ( 15 , 20 ). We previously demonstrated the role of mechanical cues in controlling hMSC epigenetic programming, linking persistent chromatin remodeling to mechanical memory induced by long-term culture on stiff hydrogel substrates ( 19 ).…”

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confidence: 99%

Nuclear mechanosensing controls MSC osteogenic potential through HDAC epigenetic remodeling

Killaars

Walker

Anseth

2020

Proc. Natl. Acad. Sci. U.S.A.

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Cells sense mechanical cues from the extracellular matrix to regulate cellular behavior and maintain tissue homeostasis. The nucleus has been implicated as a key mechanosensor and can directly influence chromatin organization, epigenetic modifications, and gene expression. Dysregulation of nuclear mechanosensing has been implicated in several diseases, including bone degeneration. Here, we exploit photostiffening hydrogels to manipulate nuclear mechanosensing in human mesenchymal stem cells (hMSCs) in vitro. Results show that hMSCs respond to matrix stiffening by increasing nuclear tension and causing an increase in histone acetylation via deactivation of histone deacetylases (HDACs). This ultimately induces osteogenic fate commitment. Disrupting nuclear mechanosensing by disconnecting the nucleus from the cytoskeleton up-regulates HDACs and prevents osteogenesis. Resetting HDAC activity back to healthy levels rescues the epigenetic and osteogenic response in hMSCs with pathological nuclear mechanosensing. Notably, bone from patients with osteoarthritis displays similar defective nuclear mechanosensing. Collectively, our results reveal that nuclear mechanosensing controls hMSC osteogenic potential mediated by HDAC epigenetic remodeling and that this cellular mechanism is likely relevant to bone-related diseases.

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“…го Российской ассоциацией по остеопорозу как без, так и с учетом минеральной плотности кости (МПК) [1], созданного в соответствии с европейскими рекомендациями по диагностике и ведению больных с постменопаузальным остеопорозом [2]. Диагноз ОП ставился по критериям ВОЗ при проведении DXA.…”

Section: диагностические возможности различных методов выделения попуunclassified

Epigenetic Regulation in Bone Tissue

Nikitin¹,

Belaya²,

Brovkina³

et al. 2016

Osteopor Bone Dis

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Epigenetic regulation of bone cells

Cited by 30 publications

References 157 publications

Lycopene improves the efficiency of anti-PD-1 therapy via activating IFN signaling of lung cancer cells

Lycopene improves the efficiency of anti-PD-1 therapy via activating IFN signaling of lung cancer cells

Nuclear mechanosensing controls MSC osteogenic potential through HDAC epigenetic remodeling

Epigenetic Regulation in Bone Tissue

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