Investigating the Impact of Circulating MicroRNAs on Knee and Hip Osteoarthritis: Causal Links, Biological Mechanisms, and Drug Interactions DOI Open Access

Shanni Li,

Y PENG,

Yang Yu

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 283 - 283

Опубликована: Дек. 31, 2024

Osteoarthritis (OA), particularly in the knee and hip, poses a significant global health challenge due to limited therapeutic options. To elucidate molecular mechanisms of OA identify potential biomarkers targets, we utilized genome-wide association studies (GWAS) cis-miRNA expression quantitative trait loci (cis-miR-eQTL) datasets miRNAs associated with OA, revealing 16 that were linked 21 hip OA. Among these, hsa-miR-1303 was significantly upregulated both (IVW: p = 6.8164×10−36 4.7919×10−2 respectively, OR > 1) identified as key factor disease progression. Hsa-miR-1303 potentially regulates 30 genes involved critical signaling pathways, such neurotrophin pathway, interacts competing endogenous RNAs (ceRNAs) like circ_0041843 LINC01338, thereby influencing regulatory proteins SUMO2 PARP1. Pharmacologically, targets nine druggable genes, including NRAS, H2AZ1, RPS3, which have implications for drugs cantharidin diindolylmethane, developing novel treatments. Conversely, hsa-miR-125a-5p hsa-miR-125b-5p, are downregulated pathways HIF-1 JAK-STAT, modulate apoptotic transcriptional regulation. These also interact ceRNAs circ_0000254 SPACA6P-AS, impacting STAT3, MCL1, TRAF6. A drug interaction analysis 47 treatments, Resveratrol Acetaminophen, suggesting new possibilities management. This study not only highlights role hsa-miR-125 but opens avenues miRNA-based development.

Язык: Английский

The emerging role of Piezo1 in the musculoskeletal system and disease DOI Creative Commons
Lei Lei,

Zhenkang Wen,

Mingde Cao

и другие.

Theranostics, Год журнала: 2024, Номер 14(10), С. 3963 - 3983

Опубликована: Янв. 1, 2024

Piezo1, a mechanosensitive ion channel, has emerged as key player in translating mechanical stimuli into biological signaling. Its involvement extends beyond physiological and pathological processes such lymphatic vessel development, axon growth, vascular immunoregulation, blood pressure regulation. The musculoskeletal system, responsible for structural support, movement, homeostasis, recently attracted attention regarding the significance of Piezo1. This review aims to provide comprehensive summary current research on Piezo1 highlighting its impact bone formation, myogenesis, chondrogenesis, intervertebral disc tendon matrix cross-linking, physical activity. Additionally, we explore potential targeting therapeutic approach disorders, including osteoporosis, muscle atrophy, degeneration, osteoarthritis.

Язык: Английский

Процитировано

4
Matrix stiffening induces hepatocyte functional impairment and DNA damage via the Piezo1‒ERK1/2 signaling pathway DOI

Yanan Fan,

Cheng Rui An,

Zhihui Wang

и другие.

Journal of Physiology and Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Язык: Английский

Процитировано

0
Revealing the mediating mechanisms between BMI and osteoarthritis: a Mendelian randomization and mediation analysis DOI Creative Commons
Hui Yu, Junxiang Wang, Xin Xu

и другие.

Aging Clinical and Experimental Research, Год журнала: 2025, Номер 37(1)

Опубликована: Апрель 7, 2025

Despite well-documented associations between Body mass index (BMI) and Osteoarthritis (OA), the specific biological pathways mediators involved remain poorly understood. This study aims to explore through which BMI influences OA risk, particularly knee osteoarthritis (KOA), using Mendelian Randomization (MR) mediation analysis. We used a two-step MR approach with data from IEU OpenGWAS FinnGen version 7 databases. (N = 322,154) was primary exposure, disorders (KD), total bone mineral density (TBMD), metabolic (MD), anxiety (AD) as potential mediators. Outcomes included KOA 22,347), hip (HOA) 11,989), all (AllOA) 50,508). Univariate evaluated causal relationships, followed by multivariate quantify effects. Multiple sensitivity analyses were conducted validate robustness, while horizontal pleiotropy heterogeneity assessed MR-Egger intercept Cochran's Q statistic. significantly increased risk of (odds ratio [OR]: 2.00, 95% confidence interval [CI]: 1.56-2.56), HOA (OR: 2.05, CI: 1.40-2.98), AllOA 1.66, 1.41-1.95). KD TBMD mediated effect on KOA, proportions 20.89% 3.59%, respectively. MD AD showed no significant Sensitivity supported robustness these findings. Horizontal tests indicated minimal evidence bias, supporting reliability our results. increases partially mediating effect, for KOA. The direct impact remains predominant, emphasizing importance weight reduction, joint protection, physical activity preventive measures.

Язык: Английский

Процитировано

0
Sex specific knee joint soft tissue mineralization with Fibrillin-1 mutation in male Tight Skin mice. DOI Creative Commons
Craig Keenan, Xi Wang, Tayfun DİKMEN

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

Abstract Articular soft tissue mineralization and ossification are clear pathological signs of osteoarthritis joints. However their molecular cellular aetiologies remain largely unknown. TGF-ß family members known contributors to both development. In this study, we used a Fibrillin-1 mutant mouse, the Tight Skin mouse (TSK), define detrimental effects abnormal Fbn1 in TSK mice high activity joint pathology such as articular ossification. Knee joints male Female Wild-type (WT) littermates were analysed my micro-CT imaging histology for pathologies, well OA severity. Both aged (10, 26, 35 52wks) following vivo non-invasive repetitive overloading used. We find that develop spontaneous from 26wks age, followed by increased at 1 year-old. addition, knee induced ligament meniscal mineralisation WT mice, but significantly more severe knees, including patella synovial lining. contrast, female knees did not compared littermate neither nor overloaded knees. conclude mutation, possibly overactive induce sex-specific manner. Further studies needed confirm specific signalling involved relative protection pathologies.

Язык: Английский

Процитировано

0
Editorial: The role of Piezo 1 in osteoarthritis: Implications for pathogenesis and therapy DOI

Shangqi Guan,

Yifang Mei

International Journal of Rheumatic Diseases, Год журнала: 2024, Номер 27(10)

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

0
Exosomal miRNA reprogramming in pyroptotic macrophage drives silica-induced fibroblast-to-myofibroblast transition and pulmonary fibrosis DOI
Zhang Lin,

Jiaqi Tian,

Ning Li

и другие.

Journal of Hazardous Materials, Год журнала: 2024, Номер 483, С. 136629 - 136629

Опубликована: Ноя. 22, 2024

Язык: Английский

Процитировано

0
Molecular basis of senescence in osteoarthritis DOI
Mandy Lawson,

Heather M. Ritchison

Опубликована: Ноя. 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

Язык: Английский

Процитировано

0
Investigating the Impact of Circulating MicroRNAs on Knee and Hip Osteoarthritis: Causal Links, Biological Mechanisms, and Drug Interactions DOI Open Access

Shanni Li,

Y PENG,

Yang Yu

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 283 - 283

Опубликована: Дек. 31, 2024

Osteoarthritis (OA), particularly in the knee and hip, poses a significant global health challenge due to limited therapeutic options. To elucidate molecular mechanisms of OA identify potential biomarkers targets, we utilized genome-wide association studies (GWAS) cis-miRNA expression quantitative trait loci (cis-miR-eQTL) datasets miRNAs associated with OA, revealing 16 that were linked 21 hip OA. Among these, hsa-miR-1303 was significantly upregulated both (IVW: p = 6.8164×10−36 4.7919×10−2 respectively, OR > 1) identified as key factor disease progression. Hsa-miR-1303 potentially regulates 30 genes involved critical signaling pathways, such neurotrophin pathway, interacts competing endogenous RNAs (ceRNAs) like circ_0041843 LINC01338, thereby influencing regulatory proteins SUMO2 PARP1. Pharmacologically, targets nine druggable genes, including NRAS, H2AZ1, RPS3, which have implications for drugs cantharidin diindolylmethane, developing novel treatments. Conversely, hsa-miR-125a-5p hsa-miR-125b-5p, are downregulated pathways HIF-1 JAK-STAT, modulate apoptotic transcriptional regulation. These also interact ceRNAs circ_0000254 SPACA6P-AS, impacting STAT3, MCL1, TRAF6. A drug interaction analysis 47 treatments, Resveratrol Acetaminophen, suggesting new possibilities management. This study not only highlights role hsa-miR-125 but opens avenues miRNA-based development.

Язык: Английский

Процитировано

0