The role of m6A in angiogenesis and vascular diseases DOI Creative Commons
Ke Chen, Wendong Li, Xiaoqiang Li

и другие.

iScience, Год журнала: 2024, Номер 27(7), С. 110082 - 110082

Опубликована: Май 23, 2024

Angiogenesis, whether physiological or pathological, plays a pivotal role in various and disease conditions. This intricate process relies on complex meticulously orchestrated signal transduction network that connects endothelial cells, their associated parietal cells (VSMCs pericytes), other cell types, including immune cells. Given the significance of m6A its connection to angiogenesis vascular disease, researchers must adopt comprehensive ongoing approach investigations. study aims ascertain common key mechanism exists diseases elucidate potential application treating diseases.

Язык: Английский

Alkbh1‐mediated DNA N6‐methyladenine modification regulates bone marrow mesenchymal stem cell fate during skeletal aging DOI Creative Commons

Guangping Cai,

Yalin Liu, Liping Luo

и другие.

Cell Proliferation, Год журнала: 2022, Номер 55(2)

Опубликована: Янв. 11, 2022

DNA N6-methyladenine (N6-mA) demethylase Alkbh1 participates in regulating osteogenic differentiation of mesenchymal stem cell (MSCs) and vascular calcification. However, the role bone metabolism remains unclear.Bone marrow cells (BMSCs)-specific knockout mice were used to investigate metabolism. Western blot, qRT-PCR, immunofluorescent staining evaluate expression or optineurin (optn). Micro-CT, histomorphometric analysis, calcein double-labeling assay phenotypes. Cell qRT-PCR adipogenic BMSCs. Dot blotting was detect level N6-mA genomic DNA. Chromatin immunoprecipitation (Chip) assays identify critical targets Alkbh1. adeno-associated virus overexpress aged mice.Alkbh1 BMSCs declined during aging. Knockout promoted while inhibited differentiation. BMSC-specific exhibited reduced mass increased adiposity. Mechanistically, we identified optn as downstream target through which Alkbh1-mediated m6A modification regulated fate. Overexpression attenuated loss fat accumulation mice.Our findings demonstrated that fate bone-fat balance skeletal aging provided a potential for treatment osteoporosis.

Язык: Английский

Процитировано

40
S-sulfhydration of SIRT3 combats BMSC senescence and ameliorates osteoporosis via stabilizing heterochromatic and mitochondrial homeostasis DOI Creative Commons
Fei Liu, Longhui Yuan, Lan Li

и другие.

Pharmacological Research, Год журнала: 2023, Номер 192, С. 106788 - 106788

Опубликована: Май 3, 2023

Senescence of bone marrow mesenchymal stem cells (BMSCs) is one the leading causes osteoporosis. SIRT3, an essential NAD-dependent histone deacetylase, highly correlated with BMSC senescence-mediated degradation and mitochondrial/heterochromatic disturbance. S-sulfhydration cysteine residues favorably enhances SIRT3 activity by forming persulfides. Nevertheless, underlying molecular mechanism on homeostasis involved in senescence remains unknown. Here, we demonstrated that CBS CSE, endogenous hydrogen sulfide synthases, are downregulated senescence. Exogenous H2S donor NaHS-mediated augmentation rescued senescent phenotypes BMSCs. Conversely, deletion accelerated oxidative stress-induced through mitochondrial dysfunction detachment heterochromatic protein H3K9me3 from nuclear envelope Lamin B1. H2S-mediated modification disorganized heterochromatin fragmented mitochondria induced inhibitor dithiothreitol, thus to elevated osteogenic capacity preventing The antisenescence effect BMSCs was abolished when CXXC sites zinc finger motif were mutated. In vivo, aged mice-derived pretreated NaHS orthotopically transplanted ovariectomy-induced osteoporotic mice, proved ameliorates loss inhibiting Overall, our study for first time indicates a novel role stabilizing counteracting senescence, providing potential target treatment degenerative diseases.

Язык: Английский

Процитировано

39
WTAP-mediated m6A modification modulates bone marrow mesenchymal stem cells differentiation potential and osteoporosis DOI Creative Commons
Yunhao You, Jincheng Liu, Lu Zhang

и другие.

Cell Death and Disease, Год журнала: 2023, Номер 14(1)

Опубликована: Янв. 17, 2023

Abstract An imbalance in the differentiation potential of bone marrow mesenchymal stem cells (BMSCs) is an important pathogenic mechanism underlying osteoporosis (OP). N6-methyladenosine (m 6 A) most common post-transcriptional modification eukaryotic cells. The role Wilms’ tumor 1-associated protein (WTAP), a member m A functional family, regulating BMSCs remains unknown. We used patient-derived and mouse model-derived samples, qRT-PCR, western blot assays, ALP activity assay, ALP, Alizarin Red staining to determine changes mRNA levels genes proteins associated with differentiation. Histological analysis micro-CT were evaluate developmental bone. results determined that WTAP promoted osteogenic inhibited adipogenic BMSCs. co-immunoprecipitation (co-IP), RNA immunoprecipitation (RIP), methylated (MeRIP), pulldown, dual-luciferase assay explore direct mechanism. Mechanistically, expression increased during significantly pri-miR-181a pri-miR-181c methylation, which was recognized by YTHDC1, maturation miR-181a miR-181c. MiR-181a miR-181c SFRP1, promoting Our demonstrated WTAP/YTHDC1/miR-181a miR-181c/SFRP1 axis regulated fate BMSCs, suggesting it might be therapeutic target for osteoporosis.

Язык: Английский

Процитировано

37
METTL3-mediated m6A modification increases Hspa1a stability to inhibit osteoblast aging DOI Creative Commons
Yaobin Wang,

Yi Chen,

Hefang Xiao

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Март 27, 2024

Abstract Senile osteoporosis is mainly caused by osteoblasts attenuation, which results in reduced bone mass and disrupted remodeling. Numerous studies have focused on the regulatory role of m6A modification osteoporosis; however, most investigated differentiation marrow mesenchymal stem cells (BMSCs), while direct mechanism remains unknown. This study revealed that progression senile closely related to downregulation methyltransferase-like 3 (METTL3). Overexpression METTL3 inhibits osteoblast aging. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) upregulates stability Hspa1a mRNA, thereby inhibiting Moreover, demonstrated enhances mRNA via regulate Notably, YTH N6-methyladenosine binding protein 2 (YTHDF2) participates stabilizing METTL3-mediated process, rather than well-known degradation function. Mechanistically, increases a YTHDF2-dependent manner inhibit Our confirmed significant aging suggested could be potential therapeutic target for osteoporosis.

Язык: Английский

Процитировано

10
Rejuvenation of BMSCs senescence by pharmacological enhancement of TFEB-mediated autophagy alleviates aged-related bone loss and extends lifespan in middle aged mice DOI Creative Commons
Ziwei Luo,

Wanyi Wei,

Dawei Qiu

и другие.

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Авг. 21, 2024

Bone marrow stromal/stem cells (BMSCs) are generally considered as common progenitors for both osteoblasts and adipocytes in the bone marrow, but show preferential differentiation into rather than under aging, thus leading to senile osteoporosis. Accumulated evidences indicate that rejuvenation of BMSCs by autophagic enhancement delays aging. Here we synthetized demonstrated a novel autophagy activator, CXM102 could induce aged BMSCs, resulting BMSCs. Furthermore, significantly stimulated anabolism, reduced adipocytes, delayed loss middle-age male mice. Mechanistically, promoted transcription factor EB (TFEB) nuclear translocation favored formation vitro vivo. Moreover, decreased serum levels inflammation organ fibrosis, prolonger lifespan Our results indicated be used an inducer rejuvenate shed new lights on strategies osteoporosis healthyspan improvement.

Язык: Английский

Процитировано

8
Accumulation of advanced oxidation protein products aggravates bone-fat imbalance during skeletal aging DOI Creative Commons

Yu‐Sheng Huang,

Jiawen Gao,

Rui-Feng Ao

и другие.

Journal of Orthopaedic Translation, Год журнала: 2025, Номер 51, С. 24 - 36

Опубликована: Янв. 21, 2025

Язык: Английский

Процитировано

1
Epigenetic regulation of B cells and its role in autoimmune pathogenesis DOI Creative Commons
Fan Xiao, Ke Rui, Xiaofei Shi

и другие.

Cellular and Molecular Immunology, Год журнала: 2022, Номер 19(11), С. 1215 - 1234

Опубликована: Окт. 12, 2022

Abstract B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although previous studies have shown many genetic polymorphisms associated with B-cell activation patients various disorders, progress epigenetic research has revealed new mechanisms leading to hyperactivation. Epigenetic mechanisms, including those involving histone modifications, DNA methylation, and noncoding RNAs, regulate responses, their dysregulation can contribute Patients diseases show alterations that lead initiation perpetuation inflammation. Moreover, clinical animal model promising potential therapies for patients. In this review, we present an up-to-date overview focus on roles regulating functional subsets. Furthermore, discuss highlight its contribution development Based preclinical evidence, novel biomarkers disorders.

Язык: Английский

Процитировано

36
The crucial mechanism and therapeutic implication of RNA methylation in bone pathophysiology DOI
Chuan Yang, Zicai Dong,

Zhiguo Ling

и другие.

Ageing Research Reviews, Год журнала: 2022, Номер 79, С. 101641 - 101641

Опубликована: Май 13, 2022

Язык: Английский

Процитировано

29
Epigenetic control of mesenchymal stem cells orchestrates bone regeneration DOI Creative Commons
Xiaofeng Wang, Fanyuan Yu, Ling Ye

и другие.

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 6, 2023

Recent studies have revealed the vital role of MSCs in bone regeneration. In both self-healing regeneration processes and biomaterial-induced healing defects beyond critical size, show several functions, including osteogenic differentiation thus providing seed cells. However, adverse factors such as drug intake body senescence can significantly affect functions Currently, modalities been developed to regulate MSCs’ phenotype promote process. Epigenetic regulation has received much attention because its heritable nature. Indeed, epigenetic is involved pathogenesis a variety disorders metabolism. Moreover, using treat diseases are also being reported. At same time, effects on yet be fully understood. This review focuses recent advances differentiation, proliferation, cellular MSCs. We intend illustrate how orchestrates process

Язык: Английский

Процитировано

16
Rejuvenation of Mesenchymal Stem Cells to Ameliorate Skeletal Aging DOI Creative Commons
Mingjia Cheng, Weihao Yuan, Alireza Moshaverinia

и другие.

Cells, Год журнала: 2023, Номер 12(7), С. 998 - 998

Опубликована: Март 24, 2023

Advanced age is a shared risk factor for many chronic and debilitating skeletal diseases including osteoporosis periodontitis. Mesenchymal stem cells develop various aging phenotypes the onset of senescence, intrinsic loss regenerative potential exacerbation inflammatory microenvironment via secretory factors. This review elaborates on emerging concepts molecular epigenetic mechanisms MSC such as accumulation oxidative stress, DNA damage mitochondrial dysfunction. Senescent MSCs aggravate local inflammation, disrupt bone remodeling bone-fat balance, thereby contributing to progression age-related diseases. Various rejuvenation strategies target senescent could present promising paradigm restore aging.

Язык: Английский

Процитировано

13