Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis

Jing, Huan; Su, Xiaoxia; Gao, Bo; Yi, Siyan; Chen, Ji Hua; Deng, Zhihong; Liao, Li; Jin, Yan

doi:10.1038/s41419-017-0231-0

Cited by 112 publications

(96 citation statements)

References 35 publications

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“…Treatment of 10T1/2 cells with vulpinic acid significantly increased the mRNA level of the three Wnt genes ( Figure 2B). A recent study showed that an increase in H3 acetylation enhances the transcription of Wnt genes promoting osteogenic differentiation of bone marrow-derived MSCs [23]. As expected, our ChIP-qPCR data showed that the enrichment of acetylated H3 on the promoter region of Wnt6, 10a, and 10b was largely increased upon vulpinic acid treatment ( Figure 2C).…”

Section: Vulpinic Acid Promotes the Expression Of Wnt Genes Via H3 Acsupporting

confidence: 86%

“…transcription of Wnt genes promoting osteogenic differentiation of bone marrow-derived MSCs [23]. As expected, our ChIP-qPCR data showed that the enrichment of acetylated H3 on the promoter region of Wnt6, 10a, and 10b was largely increased upon vulpinic acid treatment ( Figure 2C).…”

Section: Vulpinic Acid Promotes the Expression Of Wnt Genes Via H3 Acsupporting

confidence: 81%

“…To estimate the effects of vulpinic acid on the cell fate conversion of 10T1/2 MSCs, we examined the expression of Wnt genes, which are important for the determination of cell lineage during the commitment step of multipotent stem cells [21,22]. Wnt6, 10a, and 10b promote osteogenic commitment, preventing cells from entering the adipogenic commitment [21][22][23] (Figure 2A). Treatment of 10T1/2 cells with vulpinic acid significantly increased the mRNA level of the three Wnt genes ( Figure 2B).…”

Section: Vulpinic Acid Promotes the Expression Of Wnt Genes Via H3 Acmentioning

confidence: 99%

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Vulpinic Acid Controls Stem Cell Fate toward Osteogenesis and Adipogenesis

Nam

Kim

et al. 2019

Genes

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Vulpinic acid, a naturally occurring methyl ester of pulvinic acid, has been reported to exert anti-fungal, anti-cancer, and anti-oxidative effects. However, its metabolic action has not been implicated yet. Here, we show that vulpinic acid derived from a mushroom, Pulveroboletus ravenelii controls the cell fate of mesenchymal stem cells and preadipocytes by inducing the acetylation of histone H3 and α-tubulin, respectively. The treatment of 10T1/2 mesenchymal stem cells with vulpinic acid increased the expression of Wnt6, Wnt10a, and Wnt10b, which led to osteogenesis inhibiting the adipogenic lineage commitment, through the upregulation of H3 acetylation. By contrast, treatment with vulpinic acid promoted the terminal differentiation of 3T3-L1 preadipocytes into mature adipocytes. In this process, the increase in acetylated tubulin was accompanied, while acetylated H3 was not altered. As excessive generation of adipocytes occurs, the accumulation of lipid drops was not concentrated, but dispersed into a number of adipocytes. Consistently, the expressions of lipolytic genes were upregulated and inflammatory factors were downregulated in adipocytes exposed to vulpinic acid during adipogenesis. These findings reveal the multiple actions of vulpinic acid in two stages of differentiation, promoting the osteogenesis of mesenchymal stem cells and decreasing hypertrophic adipocytes, which can provide experimental evidence for the novel metabolic advantages of vulpinic acid.

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Section: Vulpinic Acid Promotes the Expression Of Wnt Genes Via H3 Acsupporting

confidence: 86%

Section: Vulpinic Acid Promotes the Expression Of Wnt Genes Via H3 Acsupporting

confidence: 81%

Section: Vulpinic Acid Promotes the Expression Of Wnt Genes Via H3 Acmentioning

confidence: 99%

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Vulpinic Acid Controls Stem Cell Fate toward Osteogenesis and Adipogenesis

Nam

Kim

et al. 2019

Genes

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“…BMSC are osteoprogenitors, which can differentiate into matured osteoblasts. A deficiency in osteoblastogenesis from BMSC is observed to result in osteoporosis . Therefore, stimulation of proliferation and osteoblastogenesis from BMSC becomes a therapeutic strategy for osteoporosis …”

Section: Introductionmentioning

confidence: 99%

Effect of hydroxyapatite nanoparticles and wedelolactone on osteoblastogenesis from bone marrow mesenchymal stem cells

Dong

Zhu

Deng

et al. 2018

J Biomedical Materials Res

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Regenerative medicine has a high demand for the development of scaffold materials combined with other osteogenic inducers to generate bioactive composite materials for bone replacement therapies. Previously, we reported that wedelolactone promoted osteoblastogenesis of bone marrow mesenchymal stem cells (BMSCs). In this study, the effect of hydroxyapatites (HAps), bone composite materials we prepared, and the combined effect of wedelolactone and HAps on osteoblastogenesis differentiation was first evaluated. Three kinds of HAps constructed by a rod-like shape with particle size of 25 nm (HAp-1), 37 nm (HAp-2), and 33 nm (HAp-3) did not affect BMSC survival, but induced activity of alkaline phosphatase(ALP), a marker enzyme for osteoblastogenesis. HAp-1 treatment resulted in a more significant increase in the number of ALP staining-positive BMSC, and maintained an extended time for the increased number of ALP stainingpositive BMSC. Moreover, HAp-1 combined with wedelolactone induced a higher ALP activity for a longer time than HAp-2 and HAp-3, and also increased the bone mineralization level. Osteoblastogenesis-related marker genes expression including osteorix, osteocalcin, and runx2 were increased after BMSC were treated with HAp-1 for 6 days. Although three kinds of HAps treatment for 9 days increased osteorix mRNA expression, osteocalcin, and runx2 mRNA expression levels were upregulated only by HAp-1. Similarly, only HAp-1 enhanced wedelolactone-induced osteocalcin, osteorix, and runx2 mRNA expression after 9 days treatment. Together, these results suggested that HAps with different sizes generated different effect on osteoblastogenesis. HAp-1 combined with wedelolacone can exert an enhanced effect on osteoblastogenesis, which has potential for treating osteoporosis.

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“…Further protein modification (e.g. disrupted histone acetylation) in BMSC leads to bone formation defects during osteoporosis. Pathways directly related to bone metabolism, such as osteoclast differentiation and calcium absorption, might help to determine the proteins composition in osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Discovery and Identification of Serum Succinyl‐Proteome for Postmenopausal Women with Osteoporosis and Osteopenia

Zhang

Liu

et al. 2019

Orthopaedic Surgery

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Objective For the purpose of providing evidence for the treatment of osteoporosis and osteopenia, this study retrospectively identified succinylation‐modified sites and proteins in postmenopausal women, and bioinformatics analysis were performed. Methods From January 2016 to June 2018, a total of 30 postmenopausal women aged from 55 to 70 years old were assigned to three groups: 10 cases with osteoporosis; 10 cases with osteopenia; and 10 cases with normal bone mass. Subsequently, the serum samples were collected from all cases for succinyl‐proteome. Measures comprised label‐free quantitative analysis, succinylation enrichment techniques, the liquid chromatograph–mass spectrometer/mass spectrometer (LC‐MS/MS) methods, and bioinformatics. Results A total of 113 succinylation sites on 35 proteins were identified based on quantitative information. The variation of the different multiple folds were more than 1.2 times as a significant increase for up‐regulated and less than 1/1.2 times as a significant decrease for down‐regulated. Among the quantified succinylation sites, 66 were up‐regulated and 11 down‐regulated in the Osteopenia/Normal comparison group, 24 were up‐regulated and 44 down‐regulated in the Osteoporosis/Osteopenia comparison group, 45 were up‐regulated and 32 down‐regulated in the Osteoporosis/Normal comparison group. Among the quantified succinylation proteins, 24 were up‐regulated and 7 down‐regulated in the Osteopenia/Normal comparison group, 15 were up‐regulated and 20 down‐regulated in the Osteoporosis/Osteopenia comparison group, 20 were up‐regulated and 17 down‐regulated in the Osteoporosis/Normal comparison group. The percentage of proteins differed in immune response, signaling pathway, proteolysis, lymphocyte, leukocyte, and cell activation. Four differentially expressed proteins (apolipoprotein A‐I, apolipoprotein A‐II, hemoglobin subunit alpha, and haptoglobin) contained quantitative information; they were mediated with receptors, factors, mechanisms, that related to bone metabolism. Hemoglobin subunit alpha was screened for diagnosis of osteopenia. Conclusions The succinyl‐proteome experimental data indicated that apolipoprotein A‐I, apolipoprotein A‐II, hemoglobin subunit alpha, and haptoglobin were valuable for diagnosis and treatment in postmenopausal women with osteoporosis and osteopenia.

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Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis

Cited by 112 publications

References 35 publications

Vulpinic Acid Controls Stem Cell Fate toward Osteogenesis and Adipogenesis

Vulpinic Acid Controls Stem Cell Fate toward Osteogenesis and Adipogenesis

Effect of hydroxyapatite nanoparticles and wedelolactone on osteoblastogenesis from bone marrow mesenchymal stem cells

Discovery and Identification of Serum Succinyl‐Proteome for Postmenopausal Women with Osteoporosis and Osteopenia

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