A Novel Osteogenic Activity of Suberoylanilide Hydroxamic Acid is Synergized by BMP-2

Lee, Zang Hee; Kim, Hyun-Jung; Ryoo, Hyun Mo

doi:10.11005/jbm.2015.22.2.51

Cited by 14 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 191 HDAC inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat) increases the Runx2 promoter acetylation to intrigue Runx2 expression and osteoblastogenesis, in a BMP2- dependent manner. 192 The Bmp2 promoter regions of the genes are epigenetically locked with increased CpG methylation and decreased H3K9 acetylation. 193 And CpG-demethylating agent or the HDAC inhibitor trichostatin-A renders Bmp2 expression.…”

Section: Regulation Of Bmp and Tgf-β Signaling In Bonementioning

confidence: 99%

TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

2016

View full text Add to dashboard Cite

Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-β and BMP signaling is controlled by multiple factors, including the ubiquitin–proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-β and BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-β and BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-β/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-β/BMP signaling and several critical cytokines’ signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-β/BMP signaling.

show abstract

Section: Regulation Of Bmp and Tgf-β Signaling In Bonementioning

confidence: 99%

TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

2016

View full text Add to dashboard Cite

show abstract

“…In this manner, a strategy for increasing the level of RUNX2 protein acetylation is a unique alternative to compensating for a reduced RUNX2 level. Many HDIs, such as SAHA 52 , TSA 53 , valproic acid 54 , sodium butyrate 55 , and MS-275 56 , have been indicated as therapeutics for osteopenic conditions. Among these HDIs, MS-275 has shown strong osteogenic effects in cell culture and animal studies 56 .…”

Section: Treatment Of Ccd By Inhibition Of Runx2 Deacetylationmentioning

confidence: 99%

RUNX2-modifying enzymes: therapeutic targets for bone diseases

et al. 2020

Self Cite

View full text Add to dashboard Cite

RUNX2 is a master transcription factor of osteoblast differentiation. RUNX2 expression in the bone and osteogenic front of a suture is crucial for cranial suture closure and membranous bone morphogenesis. In this manner, the regulation of RUNX2 is precisely controlled by multiple posttranslational modifications (PTMs) mediated by the stepwise recruitment of multiple enzymes. Genetic defects in RUNX2 itself or in its PTM regulatory pathways result in craniofacial malformations. Haploinsufficiency in RUNX2 causes cleidocranial dysplasia (CCD), which is characterized by open fontanelle and hypoplastic clavicles. In contrast, gain-of-function mutations in FGFRs, which are known upstream stimulating signals of RUNX2 activity, cause craniosynostosis (CS) characterized by premature suture obliteration. The identification of these PTM cascades could suggest suitable drug targets for RUNX2 regulation. In this review, we will focus on the mechanism of RUNX2 regulation mediated by PTMs, such as phosphorylation, prolyl isomerization, acetylation, and ubiquitination, and we will summarize the therapeutics associated with each PTM enzyme for the treatment of congenital cranial suture anomalies.

show abstract

“…In a study, the treatment of C57BL/6J mice with SAHA caused decreased mineralization and OPN, COL1A1, and OCN gene expression, and eventually led to bone loss in rodents [ 120 ]. In contrast, other researches showed that optimum dose of SAHA had no negative effects on bone formation and could promote osteogenesis via upregulation of Runx2 and BMP-2-dependent ALP activity in both human bone marrow MSCs and an osteoporotic mice model [ 121 , 122 ]. These contradicting results for SAHA in osteogenesis indicate that it has a dose-dependent function during osteo-differentiation.…”

Section: Epigenetic Modifiers Known As Epidrugsmentioning

confidence: 99%

Epidrugs: novel epigenetic regulators that open a new window for targeting osteoblast differentiation

et al. 2020

View full text Add to dashboard Cite

Efficient osteogenic differentiation of mesenchymal stem cells (MSCs) is a critical step in the treatment of bone defects and skeletal disorders, which present challenges for cell-based therapy and regenerative medicine. Thus, it is necessary to understand the regulatory agents involved in osteogenesis. Epigenetic mechanisms are considered to be the primary mediators that regulate gene expression during MSC differentiation. In recent years, epigenetic enzyme inhibitors have been used as epidrugs in cancer therapy. A number of studies mentioned the role of epigenetic inhibitors in the regulation of gene expression patterns related to osteogenic differentiation. This review attempts to provide an overview of the key regulatory agents of osteogenesis: transcription factors, signaling pathways, and, especially, epigenetic mechanisms. In addition, we propose to introduce epigenetic enzyme inhibitors (epidrugs) and their applications as future therapeutic approaches for bone defect regeneration.

show abstract

A Novel Osteogenic Activity of Suberoylanilide Hydroxamic Acid is Synergized by BMP-2

Cited by 14 publications

References 19 publications

TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

RUNX2-modifying enzymes: therapeutic targets for bone diseases

Epidrugs: novel epigenetic regulators that open a new window for targeting osteoblast differentiation

Contact Info

Product

Resources

About