Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation DOI Creative Commons

Lian Ren,

Shigao Cheng,

Pengcheng Kang

et al.

The Kaohsiung Journal of Medical Sciences, Journal Year: 2023, Volume and Issue: 39(11), P. 1096 - 1105

Published: Aug. 14, 2023

To investigate the regulatory mechanisms and effects of LIM SH3 protein 1 (LASP1) on osteoarthritis (OA). IL-1β was used to induce OA in cell models. Viability apoptosis chondrocytes were assessed. The expressions tumor necrsis factor-α (TNF-α) IL-6 measured by ELISA kit, Quantitative reverse transcription polymerase chain reaction (qRT-PCR) Western blot performed test expression related proteins. STRING database predict relationship between LASP1 DNA methyltransferase (DNMT1). tight junction 2 (TJP2) Gene Expression Omnibus data analyzed for differential genes. Methylation-specific PCR detected methylation TJP2 promoter region, chromatin immunoprecipitation enrichment DNMT1 region. Safranin O-Fast Green staining hematoxylin eosin determine OARSI score evaluate pathological conditions joint tissues. highly expressed IL-1β-induced Silencing promoted chondrocyte proliferation Collagen II Aggrecan inhibited apoptosis, inflammatory factors, matrix metalloprotein expression. is weakly models, promotes region interacting with DNMT1. attenuated degeneration promoting Similarly, silencing alleviate articular cartilage injury mice OA. DNMT1, thereby alleviating damage mice.

Language: Английский

Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases DOI Creative Commons
Juanjuan Han, C Wang, Haolin Yang

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(5), P. 514 - 514

Published: April 24, 2024

Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is key regulator in the expression genes multitude biological processes. m6A composed 0.1–0.4% adenylate residues, especially at beginning 3′-UTR near translation stop codon. The can be classified into three types, namely “writer”, “reader”, “eraser”. Studies have shown epigenetic modulation influences mRNA processing, nuclear export, translation, splicing. Regulated cell death (RCD) autonomous orderly cells under genetic control to maintain stability internal environment. Moreover, distorted RCDs are widely used influence course various receiving increasing attention from researchers. past few evidence indicated regulate gene thus different RCD processes, which central role etiology evolution MSDs. currently confirmed autophagy-dependent death, apoptosis, necroptosis, pyroptosis, ferroptosis, immunogenic NETotic oxeiptosis. m6A–RCD axis inflammatory response chondrocytes invasive migratory MM bone remodeling capacity, thereby influencing development This review gives complete overview regulatory functions across muscle, bone, cartilage. addition, we also discuss advances by m6A-targeted factors explore clinical application prospects therapies targeting MSD prevention treatment. These may provide new ideas directions for understanding pathophysiological mechanism MSDs treatment these diseases.

Language: Английский

Citations

3
N6‑methyladenosine methyltransferase METTL14 is associated with macrophage polarization in rheumatoid arthritis DOI Open Access
Ziheng Zhu, Lei Wan

Experimental and Therapeutic Medicine, Journal Year: 2024, Volume and Issue: 28(4)

Published: July 25, 2024

Rheumatoid arthritis (RA) is largely caused by the inflammatory response triggered macrophage polarization. Through epigenetic reprogramming, state of macrophages can be modified. Macrophage polarization associated with RNA alteration N6‑methyladenosine (m6A) methylation. However, specific function and underlying mechanisms m6A methylation in role RA remain to elucidated. The mRNA expression levels methylase genes signaling pathway components were determined present study using reverse‑transcription quantitative PCR. Methyltransferase 14 (METTL14) protein western blot analysis, cellular secretion factors ELISA flow cytometry. results demonstrated that elevated METTL14 was joint tenderness, positively correlated both C‑reactive rheumatoid factor levels. Moreover, exhibited potential prediction visual analogue scale. Pro‑inflammatory cytokines (TNF‑α) M1 markers (CD68+CD86+) also expression. Kyoto Encyclopedia Genes Genomes analysis revealed strongly MAPK pathway. Notably, JNK ERK2 a positive correlation marker, CD68+CD86+, which pro‑inflammatory factor, TNF‑α. markedly increased high‑expression group, compared low‑expression group; however, p38 ERK1 not significantly different between these groups. Collectively, peripheral blood synovial tissue patients RA, highlighting association immunoinflammatory clinical symptoms. In addition, it suggested may exacerbate downstream response, through mediating via

Language: Английский

Citations

1
RNA N6-methyladenosine modification in arthritis: New insights into pathogenesis DOI
Haowei Chen, Anran Xuan, Xiaorui Shi

et al.

Modern Rheumatology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 16, 2024

The commonest type of eukaryotic RNA modification, N6-methyladenosine (m6A), has drawn increased scrutiny in the context pathological functioning as well relevance determination stability, splicing, transportation, localization, and translation efficiency. m6A modification plays an important role several types arthritis, especially osteoarthritis rheumatoid arthritis. Recent studies have reported that regulates arthritis pathology cells, such chondrocytes synoviocytes via immune responses inflammatory through functional proteins classified writers, erasers, readers. aim this review was to highlight recent advances relevant pathogenesis detail underlying molecular mechanisms, regulatory functions, clinical applications, future perspectives with providing a foundation for research directions.

Language: Английский

Citations

1
YTHDC1 Regulates the Migration, Invasion, Proliferation, and Apoptosis of Rheumatoid Fibroblast-Like Synoviocytes DOI Creative Commons

Zhi‐wei Feng,

Chen-fei Yang,

Hefang Xiao

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 29, 2024

Rheumatoid arthritis (RA), a chronic autoimmune condition, is characterized by persistent synovial inflammation, bone degradation, and progressive joint deterioration. Despite considerable research efforts, the precise molecular mechanism underlying RA remains elusive. This investigation aims to elucidate potential role of N6-methyladenosine (m

Language: Английский

Citations

0
Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation DOI Creative Commons

Lian Ren,

Shigao Cheng,

Pengcheng Kang

et al.

The Kaohsiung Journal of Medical Sciences, Journal Year: 2023, Volume and Issue: 39(11), P. 1096 - 1105

Published: Aug. 14, 2023

To investigate the regulatory mechanisms and effects of LIM SH3 protein 1 (LASP1) on osteoarthritis (OA). IL-1β was used to induce OA in cell models. Viability apoptosis chondrocytes were assessed. The expressions tumor necrsis factor-α (TNF-α) IL-6 measured by ELISA kit, Quantitative reverse transcription polymerase chain reaction (qRT-PCR) Western blot performed test expression related proteins. STRING database predict relationship between LASP1 DNA methyltransferase (DNMT1). tight junction 2 (TJP2) Gene Expression Omnibus data analyzed for differential genes. Methylation-specific PCR detected methylation TJP2 promoter region, chromatin immunoprecipitation enrichment DNMT1 region. Safranin O-Fast Green staining hematoxylin eosin determine OARSI score evaluate pathological conditions joint tissues. highly expressed IL-1β-induced Silencing promoted chondrocyte proliferation Collagen II Aggrecan inhibited apoptosis, inflammatory factors, matrix metalloprotein expression. is weakly models, promotes region interacting with DNMT1. attenuated degeneration promoting Similarly, silencing alleviate articular cartilage injury mice OA. DNMT1, thereby alleviating damage mice.

Language: Английский

Citations

1