Simultaneously Modulating HIF-1α and HIF-2α and Optimizing Macrophage Polarization through the Biomimetic Gene Vector toward the Treatment of Osteoarthritis DOI Creative Commons
Boyuan Zheng,

Yiwan Shi,

Lei Xiao

et al.

Biomaterials Research, Journal Year: 2024, Volume and Issue: 28

Published: Jan. 1, 2024

In osteoarthritis (OA), articular cartilage is continuously submerged in a hypoxic environment throughout life, and hypoxia-inducible factors (HIFs) play crucial role OA progression. Among the various HIF phenotypes, HIF-1α positively contributes to maintaining stability of matrix. contrast, HIF-2α has detrimental effect, leading chondrocyte apoptosis exacerbating inflammation. Notably, there currently no simultaneous regulation for treatment. Thus, biomimetic gene vector (MENP) was developed co-delivery siHIF-2α Mg2+ inflamed regions joints, comprising an inner core consisting outer M2 macrophage membrane. vitro vivo studies demonstrate that MENP effectively targets areas, efficiently silences HIF-2α, facilitates HIF-1α-mediated restoration through Mg2+. Furthermore, it indirectly promotes polarization macrophages toward anti-inflammatory phenotype its action on synoviocytes. Overall, efficient vehicle alleviating inflammation promoting repair, representing appealing approach

Language: Английский

The role of HIF-1α in hypoxic metabolic reprogramming in osteoarthritis DOI Creative Commons
Jie Zhang,

Peng Gao,

Weirong Chang

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107649 - 107649

Published: Feb. 1, 2025

The joint dysfunction caused by osteoarthritis (OA) is increasingly becoming a major challenge in global healthcare, and there currently no effective strategy to prevent the progression of OA. Therefore, better elucidating relevant mechanisms OA occurrence development will provide theoretical basis for formulating new prevention control strategies. Due long-term exposure cartilage tissue hypoxic microenvironment joints, metabolic reprogramming changes occur. Hypoxia-inducible factor-1alpha (HIF-1α), as core gene regulating hypoxia response vivo, plays an important regulatory role metabolism chondrocytes. HIF-1α adapts such glycolysis, oxidative phosphorylation (OXPHOS), amino acid metabolism, lipid In addition, also regulates macrophage polarization synovial inflammation, chondrocytes degeneration extracellular matrix (ECM) degradation, subchondral bone remodeling angiogenesis OA, affects pathophysiological Consequently, regulation has become therapeutic target this article reviews mechanism affecting chondrocyte reprogramming, focusing on summarizes potential ingredients or targets targeting order more beneficial treatment clinical drugs.

Language: Английский

Citations

2
Glycolysis: an emerging regulator of osteoarthritis DOI Creative Commons

Dingming Jiang,

Jianan Guo,

Yingquan Liu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 9, 2024

Osteoarthritis (OA) has been a leading cause of disability in the elderly and there remains lack effective therapeutic approaches as mechanisms pathogenesis progression have yet to be elucidated. As OA progresses, cellular metabolic profiles energy production are altered, emerging reprogramming highlights importance specific pathways disease progression. crucial part glucose metabolism, glycolysis bridges inflammatory dysfunctions. Moreover, glycolytic pathway is involved different areas metabolism inflammation, associated with variety transcription factors. To date, it not fully elucidated whether changes its key enzymes onset or OA. This review summarizes important role mediating inducing tissue inflammation injury, aim providing further insights into pathological functions proposing new targets for treatment

Language: Английский

Citations

11
Unraveling the crucial role of SDF-1 in osteoarthritis progression: IL6/HIF-1α positive feedback and chondrocyte ferroptosis DOI

Tengyun Yang,

Xianguang Yang, Guoliang Wang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 152, P. 114400 - 114400

Published: March 9, 2025

Language: Английский

Citations

1
KLF transcription factors in bone diseases DOI Creative Commons
Haixia Wang, Juanjuan Han, D.О. Gorbachev

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(8)

Published: March 28, 2024

Abstract Krüppel‐like factors (KLFs) are crucial in the development of bone disease. They a family zinc finger transcription that unusual containing three highly conserved structural domains interacting with DNA. It has been discovered it engages various cell functions, including proliferation, apoptosis, autophagy, stemness, invasion and migration, is for human tissues. In recent years, role KLFs physiology pathology received adequate attention. addition to regulating normal growth musculoskeletal system, participate pathological process bones joints intimately linked several skeletal illnesses, such as osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP) osteosarcoma (OS). Consequently, targeting emerged promising therapeutic approach an array disorders. this review, we summarize current literature on importance emergence regulation particular emphasis pertinent mechanisms by which regulate diseases. We also discuss need KLFs‐based medication‐targeted treatment. These endeavours offer new perspectives use disorders provide prognostic biomarkers, targets possible drug candidates

Language: Английский

Citations

8
Casticin ameliorates osteoarthritic cartilage damage in rats through PI3K/AKT/HIF-1α signaling DOI
Deren Liu, Wei Mei,

Junfeng Kang

et al.

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 391, P. 110897 - 110897

Published: Feb. 1, 2024

Language: Английский

Citations

5
Emerging technology has a brilliant future: the CRISPR-Cas system for senescence, inflammation, and cartilage repair in osteoarthritis DOI Creative Commons
Shicheng Jia,

Rongji Liang,

Jiayou Chen

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: May 2, 2024

Abstract Osteoarthritis (OA), known as one of the most common types aseptic inflammation musculoskeletal system, is characterized by chronic pain and whole-joint lesions. With cellular molecular changes including senescence, inflammatory alterations, subsequent cartilage defects, OA eventually leads to a series adverse outcomes such disability. CRISPR-Cas-related technology has been proposed explored gene therapy, offering potential gene-editing tools that are in spotlight. Considering genetic multigene regulatory mechanisms OA, we systematically review current studies on CRISPR-Cas for improving terms inflammation, damage summarize various strategies delivering CRISPR products, hoping provide new perspective treatment taking advantage technology.

Language: Английский

Citations

5
Elucidating the role of ubiquitination and deubiquitination in osteoarthritis progression DOI Creative Commons

Chenxiao Zheng,

Jiayi Chen, Yurui Wu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 9, 2023

Osteoarthritis is non-inflammatory degenerative joint arthritis, which exacerbates disability in elder persons. The molecular mechanisms of osteoarthritis are elusive. Ubiquitination, one type post-translational modifications, has been demonstrated to accelerate or ameliorate the development and progression via targeting specific proteins for ubiquitination determining protein stability localization. Ubiquitination process can be reversed by a class deubiquitinases deubiquitination. In this review, we summarize current knowledge regarding multifaceted role E3 ubiquitin ligases pathogenesis osteoarthritis. We also describe insight into processes. Moreover, highlight multiple compounds that target influence progression. discuss challenge future perspectives modulation expression enhancement therapeutic efficacy patients. conclude modulating deubiquitination could alleviate achieve better treatment outcomes

Language: Английский

Citations

12
Network pharmacology combined with experimental validation to investigate the effect of Rongjin Niantong Fang on chondrocyte apoptosis in knee osteoarthritis DOI Creative Commons
Jun Chen, Ting Zhang,

Qingqing Luo

et al.

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 29(6)

Published: April 15, 2024

Knee osteoarthritis (KOA) is a chronic degenerative disease that affects the quality of life middle‑aged and elderly individuals, one major factors leading to disability. Rongjin Niantong Fang (RJNTF) can alleviate clinical symptoms patients with KOA, but molecular mechanism underlying its beneficial effects on KOA remains unknown. Using pharmacological analysis in vitro experiments, active components RJNTF were analyzed explore their potential therapeutic targets mechanisms in KOA. The core signaling pathways by which exerts obtained from databases such as Gene Expression Omnibus, Traditional Chinese Medicine Systems Pharmacology Analysis Platform. Subsequently, chondrocyte apoptosis was modeled using hydrogen peroxide (H2O2). Cell Counting Kit‑8 assay involving poly [ADP‑ribose] polymerase‑1 (PARP1) inhibitor, DAPI staining, reverse transcription‑quantitative PCR, Annexin V‑FITC/PI staining flow cytometry, western blotting co‑immunoprecipitation used determine efficacy uncover mechanism. It found PARP1‑knockdown lentivirus, incubation PARP1 inhibitor PJ34, medium high doses significantly reduced H2O2‑induced apoptosis. Medium downregulated expression cleaved caspase‑3, PAR total proteins, well nucleus proteins apoptosis‑inducing factor (AIF) migration inhibitory (MIF), upregulated protein, cytoplasmic AIF MIF, suggesting may inhibit through PARP1/AIF pathway.

Language: Английский

Citations

4
Cartilage Homeostasis under Physioxia DOI Open Access
Yuji Arai,

Ryota Cha,

Shuji Nakagawa

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9398 - 9398

Published: Aug. 29, 2024

Articular cartilage receives nutrients and oxygen from the synovial fluid to maintain homeostasis. However, compared tissues with abundant blood flow, articular is exposed a hypoxic environment (i.e., physioxia) has an enhanced stress response. Hypoxia-inducible factors (HIFs) play pivotal role in this physioxic environment. In normoxic conditions, HIFs are downregulated, whereas they upregulated. The HIF-α family comprises three members: HIF-1α, HIF-2α, HIF-3α. Each member distinct function cartilage. osteoarthritis, which primarily caused by degeneration of cartilage, HIF-1α upregulated chondrocytes believed protect acting anabolically on it. Conversely, contrast HIF-2α exerts catabolic influence It may therefore be possible develop new treatment for OA controlling expression drugs or altering joints.

Language: Английский

Citations

4
Potential role of gut-related factors in the pathology of cartilage in osteoarthritis DOI Creative Commons
Peng Ning, Steve Lin, Yongyan Shi

et al.

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 8, 2025

Osteoarthritis (OA) is a common progressive degenerative disease. Gut microbiota (GM) and their metabolites have been closely associated with the onset, progression, pathology of OA. GM may influence cartilage directly, or indirectly by affecting gut, immune system, endocrine system. They function through classical pathways in metabolism novel that recently discovered. Some them used as targets for prevention treatment The current study sought to describe major pathological signaling OA chondrocytes potential role gut-related factors these pathways.

Language: Английский

Citations

0