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 intersection of aging and estrogen in osteoarthritis DOI Creative Commons
Aysegul Atasoy‐Zeybek,

Kelly K. Showel,

Christopher V. Nagelli

et al.

npj Women s Health, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 25, 2025

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degradation, inflammation, and pain. While multiple factors contribute to OA development, age sex are primary risk factors, particularly affecting postmenopausal women. The dramatic increase in after menopause suggests estrogen deficiency accelerates progression. This review explores the molecular mechanisms connecting aging focusing on key genes pathways identified through RNA sequencing.

Language: Английский

Citations

2
Sirt6 promotes DNA damage repair in osteoarthritis chondrocytes by activating the Keap1/Nrf2/HO-1 signaling pathway DOI

Lingwei Mao,

Qin-Yi Jiang,

Nan Meng

et al.

Cell Cycle, Journal Year: 2024, Volume and Issue: 23(2), P. 205 - 217

Published: Jan. 17, 2024

The aim of this study was to explore the effect and mechanism Sirt6 on DNA damage repair in OA chondrocytes. Cartilage tissues were collected from patients with knee arthroplasty traumatic amputation without OA. Besides, 7-week-old male C57BL/6 mice randomly divided into Control groups; CHON-001 cells corresponding groups treated 10 ng/ml interleukin (IL)-1β, respectively. Subsequently, or siNrf2 over-expressed observe senescence chondrocytes by IL-1β through nuclear factor E2-related 2 (Nrf2) signaling pathway. expression level human mouse cartilage significantly decreased. However, 24 h treatment decreased chondrocytes, induced damage, promoted cellular senescence. In addition, over-expression inhibited IL-1β-induced Moreover, overexpression activated Keap1/Nrf2/HO-1 pathway while knockdown Nrf2 anti-senescence effects IL-1β-treated may reduce activating

Language: Английский

Citations

5
In vitro study to identify ligand‐independent function of estrogen receptor‐α in suppressing DNA damage‐induced chondrocyte senescence DOI Creative Commons
Xiurui Zhang,

Shiqi Xiang,

Yiqian Zhang

et al.

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(2)

Published: Jan. 9, 2023

Abstract In osteoarthritis (OA), chondrocytes undergo many pathological alternations that are linked with cellular senescence. However, the exact pathways lead to generation of a senescence‐like phenotype in OA not clear. Previously, we found loss estrogen receptor‐α (ERα) was associated an increased senescence level human chondrocytes. Since DNA damage is common cause senescence, aimed study relationship among ERα levels, damage, and We first examined levels ERα, representative markers normal cartilage harvested from male female donors, as well mice. The influence on studied by treating doxorubicin (DOX), which often‐used DNA‐damaging agent. Next, tested potential overexpressing reducing levels. Lastly, explored interaction between nuclear factor kappa‐light‐chain‐enhancer activated B cells (NF‐κB) pathway. Results indicated contained displayed features, were accompanied significantly reduced Overexpression DOX‐treated Moreover, DOX‐induced activation NF‐κB pathway, partially reversed ERα. Taken together, our results demonstrated critical role maintaining health inhibiting This also suggests may represent new avenue prevent treat OA.

Language: Английский

Citations

11
What improvements do general exercise training and traditional Chinese exercises have on knee osteoarthritis? A narrative review based on biological mechanisms and clinical efficacy DOI Creative Commons

Xingbin Du,

Rao Fan,

Jianda Kong

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: May 22, 2024

Background Knee osteoarthritis (KOA) is a disease that significantly affects the quality of life patients, with complex pathophysiology includes degeneration cartilage and subchondral bone, synovitis, associations mechanical load, inflammation, metabolic factors, hormonal changes, aging. Objective This article aims to comprehensively review biological mechanisms clinical effects general exercise training traditional Chinese exercises (such as Tai Chi Qigong) on treatment KOA, providing references for development prescriptions. Methods A systematic search databases including PubMed, Web Science, Google Scholar, China National Knowledge Infrastructure (CNKI) was conducted, reviewing studies randomized controlled trials (RCTs), observational studies, reviews, meta-analyses. Keywords included “knee osteoarthritis,” “exercise therapy,” “physical activity,” “traditional exercise.” Results conclusion General positively KOA by such promoting blood circulation, improving metabolism inflammatory enhancing expression anti-inflammatory cytokines, reducing cell Traditional exercises, like Qigong, benefit improvement symptoms tissue repair regulating immune function alleviating joint inflammation. Clinical have shown both types can improve physical function, life, pain relief in patients KOA. Both are non-pharmacological options effectively patients’ physiological life. Future research should further explore long-term these interventions develop personalized programs based specific needs patients.

Language: Английский

Citations

4
Research Progress of Senolytic Drugs in the Treatment of Orthopedic Diseases DOI
Minjie Zhang,

Pengqiang Lou,

Dan Shou

et al.

Gerontology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 18

Published: Feb. 12, 2025

Background: Orthopedic diseases, including osteoarthritis, osteoporosis, and age-related musculoskeletal disorders, significantly impact quality of life are becoming increasingly prevalent with aging populations. A growing body evidence highlights the role cellular senescence in pathogenesis these conditions. Senescent cells (SCs), characterized by irreversible cell cycle arrest, accumulate tissues over time, contributing to inflammation, tissue degeneration, impaired regeneration. The emerging field senolytics, which aims selectively eliminate SCs, has garnered attention as a novel therapeutic strategy orthopedics. Summary: Senolytic drugs, small molecules, peptides, natural compounds, have shown promise preclinical models early clinical trials for treatment various diseases. In orthopedics, senolytics been investigated their potential ameliorate cartilage degradation, bone fragility, other degenerative changes associated aging. Recent studies demonstrated that targeting SCs can improve function, reduce promote Although majority research is still phase, positive outcomes from animal suggest senolytic drugs may offer new avenues orthopedic Key Messages: therapies hold significant treating diseases underlying contributes degeneration inflammation. Preclinical indicate enhance repair, alleviate symptoms, slow disease progression disorders. Further needed optimize drug efficacy, ensure safety, identify patient populations benefit most treatments. development could revolutionize management aging-related providing more targeted effective approach than current

Language: Английский

Citations

0
DNA Damage and Cellular Senescence in Osteoarthritis: An Unexpected Role for Interferon Regulatory Factor 1 in Chondrocyte DNA Repair DOI
Brian O. Diekman, Richard F. Loeser

Arthritis & Rheumatology, Journal Year: 2024, Volume and Issue: 76(6), P. 842 - 844

Published: Feb. 12, 2024

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by authors. Any queries (other than missing content) should be directed to corresponding author article.

Language: Английский

Citations

3
An Integrated View of Stressors as Causative Agents in OA Pathogenesis DOI Creative Commons

Joseph S. Floramo,

Vladimir Molchanov, Huadie Liu

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 721 - 721

Published: April 22, 2023

Cells in the body are exposed to dynamic external and internal environments, many of which cause cell damage. The cell's response this damage, broadly called stress response, is meant promote survival repair or remove However, not all damage can be repaired, sometimes, even worse, overtax system itself, further aggravating homeostasis leading its loss. Aging phenotypes considered a manifestation accumulated cellular defective repair. This particularly apparent primary type articular joint, chondrocytes. Articular chondrocytes constantly facing challenge stressors, including mechanical overloading, oxidation, DNA proteostatic stress, metabolic imbalance. consequence accumulation on aberrant mitogenesis differentiation, extracellular matrix production turnover, senescence, death. most severe form stress-induced chondrocyte dysfunction joints osteoarthritis (OA). Here, we summarize studies effects stressors demonstrate that molecular effectors pathways connect amplify joint OA development.

Language: Английский

Citations

4
Memantine attenuates the development of osteoarthritis by blocking NMDA receptor mediated calcium overload and chondrocyte senescence DOI Creative Commons

Qingmei Cheng,

Ke He,

Junyu Zhu

et al.

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 48, P. 204 - 216

Published: Aug. 27, 2024

Memantine, which is an FDA-proven drug for the treatment of dementia, exerts its function by blocking NMDA (N-methyl-D-aspartate) receptor, a calcium-permeable ion channel that reduces cytotoxic calcium overload. Chondrocyte senescence crucial cellular event contributes to articular cartilage degeneration during osteoarthritis (OA) development. To date, effects memantine and downstream receptor on chondrocyte OA have been rarely reported.

Language: Английский

Citations

1
Neuroendocrinology of reproductive behavior DOI
Vic Shao‐Chih Chiang, Jin‐Ho Park

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 199 - 221

Published: Jan. 1, 2024

Language: Английский

Citations

0
Anti-aging effect of extracellular vesicles from mesenchymal stromal cells on senescence-induced chondrocytes in osteoarthritis DOI Creative Commons
Jérémy Boulestreau,

Marie Maumus,

Giuliana Bertolino Minani

et al.

Aging, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Age is the most important risk factor for degenerative diseases such as osteoarthritis (OA). It associated with accumulation of senescent cells in joint tissues that contribute to pathogenesis OA, particular through release senescence-associated secretory phenotype (SASP) factors. Mesenchymal stromal (MSCs) and their derived extracellular vesicles (EVs) are promising treatments OA. However, senoprotective effects MSC-derived EVs OA have been poorly investigated. Here, we used from human adipose tissue-derived MSCs (ASC-EVs) two models inflammaging (IL1β)- DNA damage (etoposide)-induced senescence chondrocytes. We showed addition ASC-EVs was effective reducing parameters, including number SA-β-Gal-positive cells, γH2AX foci nuclei secretion SASP In addition, demonstrated therapeutic efficacy when injected into a murine model Several markers senescence, inflammation oxidative stress were decreased shortly after injection likely explaining efficacy. conclusion, exert function both in vitro, induced chondrocytes and, vivo, collagenase-induced

Language: Английский

Citations

0