Molecular basis of senescence in osteoarthritis DOI
Mandy Lawson,

Heather M. Ritchison

Published: Nov. 25, 2024

Osteoarthritis (OA) is a multifaceted degenerative joint disorder with substantial global socioeconomic implications. Cellular senescence, defined by permanent cell cycle arrest, has been identified as critical contributor to OA progression, driving the disruption of cartilage homeostasis and structural integrity. Here, we first delve into molecular triggers senescence in OA, including impaired DNA damage response, telomere shortening, mitochondrial dysfunction, oxidative autophagic stresses, epigenetic modifications, dysregulated sirtuins noncoding RNAs. These factors collectively contribute establishment senescent phenotype tissues, perpetuating processes observed OA. Later, present pro-inflammatory senescence-associated secretory (SASP) force behind senescence-mediated progression that fuels chronic inflammation via release cytokines, chemokines, matrix-degrading enzymes, disrupts tissue repair mechanisms, alters microenvironment favor catabolic processes, further exacerbating degeneration. The interplay between these highlights complexity senescence-driven degeneration underscoring need for deeper insights basis disease. This review aims illuminate providing foundation understanding cellular pathways drive identifying knowledge gaps guide future research on this pervasive

Language: Английский

The Multifaceted Protective Role of Nuclear Factor Erythroid 2-Related Factor 2 in Osteoarthritis: Regulation of Oxidative Stress and Inflammation DOI Creative Commons
Weibei Sheng, Yaohang Yue, Tiantian Qi

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 6619 - 6633

Published: Sept. 1, 2024

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of cartilage, subchondral bone sclerosis, synovitis, and structural changes in joint. Recent research has highlighted role various genes pathogenesis progression OA, with nuclear factor erythroid 2-related 2 (NRF2) emerging as critical player. NRF2, vital transcription factor, plays key regulating OA microenvironment slowing disease's progression. It modulates expression several antioxidant enzymes, such Heme oxygenase-1 (HO-1) NAD(P)H oxidoreductase 1 (NQO1), among others, which help reduce oxidative stress. Furthermore, NRF2 inhibits kappa-B (NF-κB) signaling pathway, thereby decreasing inflammation, pain, breakdown cartilage extracellular matrix, while also mitigating cell aging death. This review discusses NRF2's impact on stress, aging, death modes (such apoptosis, necroptosis, ferroptosis) OA-affected chondrocytes. The macrophages, synovial fibroblasts was discussed. covers preserving matrix alleviating pain. purpose this to provide comprehensive understanding protective mechanisms highlighting its potential therapeutic target underscoring significance development novel treatment strategies for OA.

Language: Английский

Citations

4
NLRP3 Inflammasome-Mediated Osteoarthritis: The Role of Epigenetics DOI Creative Commons
Yuzhou Liu, Ying Wang,

Ping Yan

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(1), P. 71 - 71

Published: Jan. 14, 2025

The prevalence of osteoarthritis (OA) notably surges with age and weight gain. most common clinical therapeutic drugs are painkillers, yet they cannot impede the deteriorating course OA. Thus, understanding OA's pathogenesis devising effective therapies is crucial. It generally recognized that inflammation, pyroptosis, OA progression tightly linked. activation NLRP3 inflammasome can lead to discharge pro-inflammatory cytokines Interleukin-1β IL-18, intensifying subsequent inflammatory reactions promoting development. Conversely, imbalance caused by deacetylase-regulated underlies chronic mild inflammation related degenerative diseases. Therefore, this article expounds on mechanism role histone deacetylases (HDACs) in inflammasome-triggered OA, illustrates application HDAC inhibitors striving provide more insights into novel treatment approaches.

Language: Английский

Citations

0
SIRT6 inhibits endoplasmic reticulum stress-mediated ferroptosis by activating Nrf2/HO-1 signaling to alleviate osteoarthritis DOI
Jiaqi Shi, Li Chen, Xu Wang

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Feb. 10, 2025

Language: Английский

Citations

0
LncRNA TUG1 regulates miR-34a-5p / SIRT6 to participate in benzene-induced hematotoxicity through PI3K / AKT /mTOR signaling pathway DOI
Rongli Sun, Jinyan Liu,

Xiaoqin Li

et al.

Food and Chemical Toxicology, Journal Year: 2024, Volume and Issue: unknown, P. 115026 - 115026

Published: Sept. 1, 2024

Language: Английский

Citations

0
Molecular basis of senescence in osteoarthritis DOI
Mandy Lawson,

Heather M. Ritchison

Published: Nov. 25, 2024

Osteoarthritis (OA) is a multifaceted degenerative joint disorder with substantial global socioeconomic implications. Cellular senescence, defined by permanent cell cycle arrest, has been identified as critical contributor to OA progression, driving the disruption of cartilage homeostasis and structural integrity. Here, we first delve into molecular triggers senescence in OA, including impaired DNA damage response, telomere shortening, mitochondrial dysfunction, oxidative autophagic stresses, epigenetic modifications, dysregulated sirtuins noncoding RNAs. These factors collectively contribute establishment senescent phenotype tissues, perpetuating processes observed OA. Later, present pro-inflammatory senescence-associated secretory (SASP) force behind senescence-mediated progression that fuels chronic inflammation via release cytokines, chemokines, matrix-degrading enzymes, disrupts tissue repair mechanisms, alters microenvironment favor catabolic processes, further exacerbating degeneration. The interplay between these highlights complexity senescence-driven degeneration underscoring need for deeper insights basis disease. This review aims illuminate providing foundation understanding cellular pathways drive identifying knowledge gaps guide future research on this pervasive

Language: Английский

Citations

0