Inhibition of Histone Deacetylases Enhances the Osteogenic Differentiation of Human Periodontal Ligament Cells

Huynh, Nam Cong-Nhat; Everts, Vincent; Pavasant, Prasit; Ampornaramveth, Ruchanee Salingcarnboriboon

doi:10.1002/jcb.25429

Cited by 55 publications

(82 citation statements)

References 48 publications

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“…Thus, our observations suggest that vulpinic acid would be helpful in recovering the osteogenic capacities of MSCs in osteoporosis patients. Several more recent studies have reported the osteogenic effects of HDAC inhibitors [46][47][48]. In our data, the treatment of 10T1/2 MSCs with vulpinic acid increased H3 acetylation, both at the global level and at the local level, on the promoter regions of Wnt genes and the Runx2 gene.…”

Section: Discussionsupporting

confidence: 70%

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: Discussionsupporting

confidence: 70%

Vulpinic Acid Controls Stem Cell Fate toward Osteogenesis and Adipogenesis

Nam

Kim

et al. 2019

Genes

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“…Inhibition of the activity of HDACs with specific or pan HDAC inhibitors, enhances osteogenic differentiation in detriment of adipogenic differentiation in many cellular models [6,30,40]. These effects could be a consequence of the change of the acetylation state in the N-term of histone H3 and/or H4.…”

Section: Discussionmentioning

confidence: 99%

14-3-3β paralog is inhibited by acetylation during differentiation to the osteogenic lineage.

López

Gojanovich

Uhart

et al. 2020

Preprint

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Background 14-3-3 protein family binds and regulate hundreds of serine/threonine phosphorylated proteins. Considered as redundant, ubiquitous and constantly expressed, this protein family was treated as an accessory for many signaling systems. Recently, specific biological functions were discovered for each of its seven paralogs in humans. Here, we studied the reversible inhibition by acetylation of its essential N- ε -lysine 49/51 residue during the osteogenic differentiation of human adipose-derived stem cells. Methods Human adipose-derived stem cells were obtained from healthy patients who underwent a dermolipectomy. The material was processed to obtain the ASCs from the stromal vascular fraction. Proteins of interest were analyzed by confocal microscopy and Western blot, and the expression level of selected proteins were modified by using lentivirus and specific shRNAs. Results We found that during the differentiation of ASC, the levels of 14-3-3 acK49/51 increased, showing that inhibition of 14-3-3 is necessary during this process. Among the 7 paralogs of this family, the inhibition by this posttranslational modification occurs mostly on the paralog β , located specifically in the nucleus, where 14-3-3 was described to bind to H3 histone and many transcription factors. Paralog specific inhibition by short hairpin RNA showed that silencing of 14-3-3 β gene, but not 14-3-3γ, increases significantly the osteogenic potential of the cells. Transdifferentiation from osteogenic to adipogenic linage of cell lines that were specifically silenced for 14-3-3 β o γ paralogs showed that 14-3-3b could be a negative regulator of the differentiation to the osteogenic lineage. Conclusion We showed that specifically 14-3-3 β is a negative regulator of osteogenesis. The levels of its inhibition by acetylation on lysine 51 is the key cellular mechanism to regulate it. The HBO1 acetyltransferase could be the enzyme responsible of this modification. Cells were this inhibition was emulated by decreasing the levels of expression of 14-3-3 β showed significant increased potential for the differentiation to the osteogenic lineage.

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Section: Discussionmentioning

confidence: 99%

14-3-3β paralog is inhibited by acetylation during differentiation to the osteogenic lineage

Frontini-López

Gojanovich

Uhart

et al. 2019

Preprint

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14-3-3 protein family binds and regulate hundred of serine/threonine phosphorylated proteins. Considered as redundant, ubiquitous and constantly expressed this protein family was treated as an accessory for many signaling systems. Here we studied the reversible inhibition by acetylation of its essential N-ε-lysine 49/51 residue during the osteogenic differentiation of human adipose-derived stem cells (ASC). We found that during the differentiation of ASC the levels of 14-3-3 acK49/51 increase showing that inhibition of 14-3-3 is necessary for this process. Among the 7 paralogs of this family, the inhibition by this posttranslational modification occurs mostly on the paralog b located specifically in the nucleus where 14-3-3 was described to binds to H3 histone and many transcription factors. Short hairpin RNA silencing of 14-3-3 b gene but not 14-3-3g increases significantly the osteogenic potential of the cells. These results show that specifically 14-3-3b is a negative regulator of osteogenesis and its inhibition by acetylation on lysine 51 is the cellular mechanism to regulate it.

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Inhibition of Histone Deacetylases Enhances the Osteogenic Differentiation of Human Periodontal Ligament Cells

Cited by 55 publications

References 48 publications

Vulpinic Acid Controls Stem Cell Fate toward Osteogenesis and Adipogenesis

Vulpinic Acid Controls Stem Cell Fate toward Osteogenesis and Adipogenesis

14-3-3β paralog is inhibited by acetylation during differentiation to the osteogenic lineage.

14-3-3β paralog is inhibited by acetylation during differentiation to the osteogenic lineage

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