MicroRNA‑4327 regulates TGF‑β1 stimulation of matrix metalloproteinase‑13 expression via CREB‑binding protein‑mediated Runx2 acetylation in human osteoblasts DOI Open Access
Rushil Kolipaka, Induja Magesh,

S. Karthik

et al.

Experimental and Therapeutic Medicine, Journal Year: 2024, Volume and Issue: 29(1)

Published: Nov. 19, 2024

Transforming growth factor beta 1 (TGF‑β1), a multifunctional cytokine, induces the expression of bone remodeling gene matrix metalloproteinase‑13 (MMP‑13). CREB‑binding protein (CBP), co‑activator and runt‑related transcription 2 (Runx2), factor, play critical roles in regulating bone‑remodeling genes. Recent advances non‑coding RNAs have revealed significance microRNAs (miRNAs) their target genes physiology. The present study hypothesized that TGF‑β1 stimulated MMP‑13 by downregulating CBP‑targeting miRNAs activating CBP‑mediated Runx2 acetylation human osteoblastic cells. TGF‑β1‑downregulated potentially CBP were identified. Among these miRNAs, significantly downregulated miR‑4327 CBP, acetylated levels cells this effect was decreased overexpressing In cells, found to directly bind 3'‑untranslated region using dual‑luciferase reporter assay. Thus, indicated TGF‑β1/miR‑4327/CBP/Runx2 plays key role expression, suggesting clinical relevance axis for treating bone‑related disorders.

Language: Английский

Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis DOI Creative Commons
Siyu Zhu, Wei Chen,

Alasdair Masson

et al.

Cell Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 2, 2024

Abstract The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This process plays a crucial role in bone formation and homeostasis is regulated by two intricate processes: cell signal transduction transcriptional gene expression. Various essential signaling pathways, including Wnt, BMP, TGF-β, Hedgehog, PTH, FGF, Ephrin, Notch, Hippo, Piezo1/2, play critical facilitating osteoblast differentiation, formation, homeostasis. Key factors this include Runx2, Cbfβ, Runx1, Osterix, ATF4, SATB2, TAZ/YAP. Furthermore, diverse array epigenetic also roles at the level. review provides an overview latest developments current comprehension concerning pathways signaling, regulation hormones, genes involved commitment lineage, well maintenance paper reviews via mechanisms, such histone DNA modifications. Additionally, we summarize biology spurred recent advancements various modern technologies bioinformatics. By synthesizing these insights comprehensive understanding further clarification mechanisms underlying lineage commitment, highlights potential new therapeutic applications for treatment diseases.

Language: Английский

Citations

79
PKM2‐Driven Lactate Overproduction Triggers Endothelial‐To‐Mesenchymal Transition in Ischemic Flap via Mediating TWIST1 Lactylation DOI Creative Commons
Yining Xu,

Xianhui Ma,

Weiyu Ni

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Abstract The accumulation of lactate is a rising risk factor for patients after flap transplantation. Endothelial‐to‐mesenchymal transition (EndoMT) plays critical role in skin fibrosis. Nevertheless, whether overproduction directly contributes to necrosis and its mechanism remain unknown. current study reveals that mice exhibit enhanced PKM2 fibrotic response. Endothelial‐specific deletion attenuates ameliorates fibrosis mice. Administration or overexpressing promotes dysfunction endothelial cells stimulates mesenchymal‐like phenotype following hypoxia. Mechanistically, glycolytic‐lactate induces correlation between Twist1 p300/CBP, leading lactylation lysine 150 (K150la). increase K150la phosphorylation nuclear translocation further regulates the transcription TGFB1 , hence inducing phenotype. Genetically endothelial‐specific diminishes lactylation, then EndoMT‐associated ischemia. serum levels transplantation are elevated predictive value prognosis. This findings suggested novel PKM2‐derived mediating exacerbates Inhibition reduces response might become potential therapeutic strategy

Language: Английский

Citations

7
Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease DOI Creative Commons
Wei‐Shiung Lian, Re‐Wen Wu, Yu-Han Lin

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 470 - 470

Published: April 17, 2024

Imbalanced osteogenic cell-mediated bone gain and osteoclastic remodeling accelerates the development of osteoporosis, which is leading risk factor disability in elderly. Harmonizing metabolic actions bone-making cells resorbing to mineralized matrix network required maintain mass homeostasis. The tricarboxylic acid (TCA) cycle mitochondria a crucial process for cellular energy production redox canonical TCA enzymes intermediates are indispensable oxidative phosphorylation adenosine triphosphate (ATP) biosynthesis differentiation osteoclast formation. Knockout mouse models identify these enzymes’ roles microarchitecture. In noncanonical processes, metabolites as co-factor or substrate involve epigenetic modification, including histone acetyltransferases, DNA demethylases, RNA m6A affect genomic stability chromatin accessibility cell metabolism formation resorption. genetic manipulation regulators intermediate supplementation compromises age, estrogen deficiency, inflammation-induced loss microstructure deterioration. This review sheds light on functions terms integrity highlights crosstalk pathways skeletal tissue treatment options delaying osteoporosis.

Language: Английский

Citations

5
The advances in acetylation modification in senescence and aging-related diseases DOI Creative Commons
Mingliang Xu, Wenbin Wang, Saien Lu

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: May 12, 2025

Aging is a process in which organisms or cells undergo decline their functions. Epigenetic modification changes have been recognized as senescence hallmark both natural aging and stimulation-induced senescence. An acetylation dynamic process, plays crucial role the through DNA stability, metabolism, signaling pathways. We summarized regulatory pathways of modifications Various cell fate-determining proteins regulate multiple cellular processes modifications. These interact coordinate with each other, forming an integrated network framework that collectively drives via systemic mechanisms. Based on these findings, we proposed “acetylation-network regulation-cellular senescence” model, to elaborate how contributes believe this insight could provide new directions intervention strategies for aging-related diseases.

Language: Английский

Citations

0
Design, synthesis and biological evaluation of new RNF126-based p300/CBP degraders DOI
Yanhua Lei, Qing Tang, Yang Ni

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 148, P. 107427 - 107427

Published: May 4, 2024

Language: Английский

Citations

2
Unlocking the potential of histone modification in regulating bone metabolism DOI
Jiayuan Zhang, Hanghang Liu, Yao Liu

et al.

Biochimie, Journal Year: 2024, Volume and Issue: 227, P. 286 - 298

Published: Aug. 22, 2024

Language: Английский

Citations

2
3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius DOI Creative Commons
Baoxin Zhang, Zhiwei Pei,

Wanxiong He

et al.

Aging, Journal Year: 2024, Volume and Issue: 16(11), P. 9625 - 9648

Published: May 31, 2024

Currently, the repair of large bone defects still faces numerous challenges, with most crucial being lack grafts good osteogenic properties. In this study, a novel implant (degradable porous zinc scaffold/BF Exo composite implant) was developed by utilizing laser melting rapid prototyping 3D printing technology to fabricate scaffold, combining it under vacuum conditions highly bioactive serum exosomes (BF EXO) and Poloxamer 407 thermosensitive hydrogel. The electron microscope revealed presence tea saucer-shaped double-layered membrane structure, ranging in diameter from 30-150 nm, an average size 86.3 nm concentration 3.28E+09 particles/mL.

Language: Английский

Citations

0
Functional analysis of a novel pathogenic variant in CREBBP associated with bone development DOI
Qing Fang,

Yunlan Xu,

Jue Feng

et al.

Pediatric Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 31, 2024

Language: Английский

Citations

0
Early-Onset Osteoporosis: Molecular Analysis in Large Cohort and Focus on the PLS3 Gene DOI
Maxence Mancini,

Roland Chapurlat,

Bertrand Isidor

et al.

Calcified Tissue International, Journal Year: 2024, Volume and Issue: 115(5), P. 591 - 598

Published: Sept. 24, 2024

Language: Английский

Citations

0
Validation of selective catalytic BmCBP inhibitors that regulate the Bm30K‐24 protein expression in silkworm, Bombyx mori DOI Open Access

Jiasheng Geng,

Weina Lu,

Qinglong Kong

et al.

Insect Molecular Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

The cAMP response element binding protein (CREB)-binding (CBP) is a histone acetyltransferase that plays an indispensable role in regulating the acetylation of and non-histone proteins. Recently, it has been discovered chemical inhibitors A485 C646 can bind to Bombyx mori's CBP (BmCBP) inhibit its activity. Notably, ability with BmCBP showed very low Kd value 48 nM by surface plasmon resonance (SPR) test. Further identification both decrease level known substrate H3K27 only 1 μM almost completely H3K27, suggesting effective inhibitor BmCBP's Moreover, was confirmed could downregulate expression acetylated Bm30K-24 at post-translational through modification BmCBP. Additionally, found stability improve ubiquitination level, compete same lysine site on Bm30K-24, thereby affecting stability. Here, we predict may be potent which utilized activity insects, including silkworms.

Language: Английский

Citations

0