Inhibition of Histone Deacetylases Potentiates BMP9-Induced Osteogenic Signaling in Mouse Mesenchymal Stem Cells

Hu, Ning; Wang, Changdong; Liu, Xi; Liang, Yin; Luο, Xingguang; Liu, Bo; Zhang, Hongyu; Shui, Wei; Guo, Nan; Wang, Ning; Wu, Ningning; Chen, Xian; He, Yong; Wen, Sheng; Deng, Fang; Zhang, Hongmei; Zhan, Lin; Luu, Hue H.; Haydon, Rex C.; He, Tong‐Chuan; Huang, Wei

doi:10.1159/000354453

Cited by 26 publications

(13 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, histone deacetylases were found to play a critical role in BMP9-mediated osteogenic signaling in mouse mesenchymal stem cells [11]. In the present study, the in vitro development of parthenogenetic embryos was enhanced with VPA treatment.…”

Section: Discussionsupporting

confidence: 49%

Valproic Acid Improves Porcine Parthenogenetic Embryo Development Through Transient Remodeling of Histone Modifiers

Huang

Yuan

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Parthenogenetic embryos are useful in many applications, such as being an alternative source of embryonic stem cells that would avoid ethical problems. Aberrance in epigenetic reprogramming is considered the major reason for the developmental failure of parthenogenetic embryos. Many histone deacetylase inhibitors have been shown to improve the reprogramming of stem cells and embryos. Here, the relationship between histone modification and parthenogenetic embryonic development was explored. Methods: Valproic acid (VPA) treatment was applied during the culture of parthenogenetic embryos. The abundance of histone modifiers was examined by immunofluorescence and quantified by Image-pro software. Results: The acH3K9 level in in vitro fertilized embryos was significantly higher than parthenogenetic embryos. VPA treatment improved both the blastocyst formation rate and the acH3K9 level in parthenogenetic embryos. The signal intensities of acH4K5 and H3K4me2 were also enhanced in VPA treated embryos. The H3K27me2 level was decreased in the VPA treated embryos at the 2-cell stage. However, the enhancement in the acH3K9, acH4K5 and H3K4me2 level, or the decrease in the H3K27me2 level disappeared shortly after VPA withdrawal. Conclusion: Optimizing histone modifications for a short time following activation was sufficient to enhance the in vitro development of parthenogenetic embryos.

show abstract

Section: Discussionsupporting

confidence: 49%

Valproic Acid Improves Porcine Parthenogenetic Embryo Development Through Transient Remodeling of Histone Modifiers

Huang

Yuan

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Since histone acetylation contributes to osteogenic differentiation of MSCs 19 , we profiled expression of 15 histone acetylases in H-PDLSCs and P-PDLSCs. The results showed that in comparison to H-PDLSCs, KAT2A, MOZ, MORF, EP300 and HAT1 were suppressed in P-PDLSCs as assayed by qRT-PCR analysis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Osthole improves function of periodontitis periodontal ligament stem cells via epigenetic modification in cell sheets engineering

Sun

Dong

Zhang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Inflammatory microenvironment causes the change of epigenetic modification in periodontal ligament stem cells derived from periodontitis tissues (P-PDLSCs), which results in defective osteogenic differentiation compared to cells from healthy tissues. It’s urgent to explore therapeutic strategies aimed at epigenetic targets associated with the regenerative ability of PDLSCs. Osthole, a small-molecule compound extracted from Chinese herbs, has been documented to promote osteogenesis and cell sheets formation of healthy PDLSCs. However, whether osthole shows same effect on P-PDLSCs and the mechanism of promotive effect is still unknown. The purpose of this study was to determine whether Osthole could restore defective osteogenic differentiation of P-PDLSCs via epigenetic modification. We demonstrated that 10−7 Mol/L of Osthole was the best concentration for osteogenic differentiation and proliferation of P-PDLSCs. Mechanistically, we also found that Osthole upregulated MOZ and MORF, histone acetylases that specifically catalyze acetylation of Histone3 lisine9 (H3K9) and Histone3 lisine14 (H3K14), which are key regulators in osteogenic differentiation of P-PDLSCs. Furthermore, Osthole treatment improved cell sheet formation and enhanced the bone formation of PDLSC sheets in animal models of periodontitis. Our study suggests that Osthole is a promising drug to cure periodontitis via regulating epigenetic modification in cell sheets engineering.

show abstract

“…In order to precisely observe the effects of HIF-1α on the BMP2-induced progression of chondrogenesis and endochondral ossification, a fetal limb culture was performed. Fetal limb cultures can mimic the progression of chondrogenesis and endochondral ossification in vitro [38,51,52]. The results revealed that HIF-1α and BMP2 acted synergistically inin expanding the proliferating chondrocyte zone and inhibiting the BMP2-induced chondrocyte hypertrophy and endochondral ossification zone.…”

Section: Disscussionmentioning

confidence: 99%

HIF-1α as a Regulator of BMP2-Induced Chondrogenic Differentiation, Osteogenic Differentiation, and Endochondral Ossification in Stem Cells

Zhou

Liao

et al. 2015

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Joint cartilage defects are difficult to treat due to the limited self-repair capacities of cartilage. Cartilage tissue engineering based on stem cells and gene enhancement is a potential alternative for cartilage repair. Bone morphogenetic protein 2 (BMP2) has been shown to induce chondrogenic differentiation in mesenchymal stem cells (MSCs); however, maintaining the phenotypes of MSCs during cartilage repair since differentiation occurs along the endochondral ossification pathway. In this study, hypoxia inducible factor, or (HIF)-1α, was determined to be a regulator of BMP2-induced chondrogenic differentiation, osteogenic differentiation, and endochondral bone formation. Methods: BMP2 was used to induce chondrogenic and osteogenic differentiation in stem cells and fetal limb development. After HIF-1α was added to the inducing system, any changes in the differentiation markers were assessed. Results: HIF-1α was found to potentiate BMP2-induced Sox9 and the expression of chondrogenesis by downstream markers, and inhibit Runx2 and the expression of osteogenesis by downstream markers in vitro. In subcutaneous stem cell implantation studies, HIF-1α was shown to potentiate BMP2-induced cartilage formation and inhibit endochondral ossification during ectopic bone/cartilage formation. In the fetal limb culture, HIF-1α and BMP2 synergistically promoted the expansion of the proliferating chondrocyte zone and inhibited chondrocyte hypertrophy and endochondral ossification. Conclusion: The results of this study indicated that, when combined with BMP2, HIF-1α induced MSC differentiation could become a new method of maintaining cartilage phenotypes during cartilage tissue engineering.

show abstract

Inhibition of Histone Deacetylases Potentiates BMP9-Induced Osteogenic Signaling in Mouse Mesenchymal Stem Cells

Cited by 26 publications

References 58 publications

Valproic Acid Improves Porcine Parthenogenetic Embryo Development Through Transient Remodeling of Histone Modifiers

Valproic Acid Improves Porcine Parthenogenetic Embryo Development Through Transient Remodeling of Histone Modifiers

Osthole improves function of periodontitis periodontal ligament stem cells via epigenetic modification in cell sheets engineering

HIF-1α as a Regulator of BMP2-Induced Chondrogenic Differentiation, Osteogenic Differentiation, and Endochondral Ossification in Stem Cells

Contact Info

Product

Resources

About