Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 30, 2024

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal tissue structure reduced strength in patients with diabetes. Studies have revealed close association among diabetes, increased fracture risk, disturbances iron metabolism. This review explores concept of ferroptosis, non-apoptotic cell death process dependent on intracellular iron, focusing its role DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic β-cells, osteoblasts (OBs) osteoclasts (OCs), contributes to The intricate interplay between dysregulation, which comprises deficiency overload, DOP has been discussed, emphasizing how excessive accumulation triggers ferroptosis concise overview highlights need understand complex relationship T2DM OP, ferroptosis. aimed elucidate pathogenesis provide prospective for future research targeting interventions field

Язык: Английский

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Supramolecular self-assembly of EGCG-selenomethionine nanodrug for treating osteoarthritis

Bioactive Materials, Год журнала: 2023, Номер 32, С. 164 - 176

Опубликована: Окт. 9, 2023

Osteoarthritis (OA) has emerged as a significant health concern among the elderly population, with increasing attention paid to ferroptosis-induced OA in recent years. However, prolonged use of nonsteroidal anti-inflammatory drugs or corticosteroids can lead series side effects and limited therapeutic efficacy. This study aimed employ Mannich condensation reaction between epigallocatechin-3-gallate (EGCG) selenomethionine (SeMet) efficiently synthesize polyphenol-based nanodrugs aqueous media for treating OA. Molecular biology experiments demonstrated that EGCG-based (ES NDs) could effectively reduce glutathione peroxidase 4 (GPX4) inactivation, abnormal Fe2+ accumulation, lipid peroxidation induced by oxidative stress, which ameliorated metabolic disorder chondrocytes other multiple pathological processes triggered ferroptosis. Moreover, imaging histopathological analysis destabilization medial meniscus model mice confirmed ES NDs exhibiting relieving The intra-articular delivery represents promising approach joint inflammatory diseases.

Язык: Английский

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ROS‐Responsive Injectable Hydrogel Loaded with SLC7A11‐modRNA Inhibits Ferroptosis and Mitigates Intervertebral Disc Degeneration in Rats

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(27)

Опубликована: Май 1, 2024

Abstract Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, with oxidative stress being a recognized factor that causes its development. Presently, pain imposes significant global economic burden. However, effectiveness treatments for IVDD remains extremely limited. Therefore, this study aims to explore innovative and effective by focusing on as starting point. In study, an injectable reactive oxygen species‐responsive hydrogel (PVA‐tsPBA@SLC7A11 modRNA) developed, designed achieve rapid loading selective release chemically synthesized modified mRNA (modRNA). SLC7A11 modRNA specifically used upregulate expression ferroptosis marker SLC7A11. The local injection PVA‐tsPBA@SLC7A11 into degenerated intervertebral (IVD) results in cleavage PVA‐tsPBA, leading enclosed modRNA. extent directly proportional severity IVDD, ultimately ameliorating inhibiting nucleus pulposus cells (NPCs). This proposes system PVA‐tsPBA hydrogel‐encapsulated modRNA, representing potential novel treatment strategy patients early‐stage IVDD.

Язык: Английский

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GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis via Targeting TLR2/AKR1C3

International Journal of Biological Sciences, Год журнала: 2025, Номер 21(3), С. 1174 - 1186

Опубликована: Янв. 13, 2025

This study explored the role of ferroptosis in intervertebral disc degeneration (IVDD), and identified GATA6 as a key regulator this process. A ferroptosis-related gene risk coefficient model was constructed using differential expression analysis GSE70362 dataset. The significant factor IVDD progression. shown to promote nucleus pulposus cells (NPCs) by regulating AKR1C3 through TLR2 pathway. In vitro vivo experiments demonstrated that knockdown reduced ferroptosis, improved cell viability, mitigated extracellular matrix degradation, whereas overexpression exacerbated these processes. Furthermore, found be crucial for GATA6-mediated modulation TLR2-AKR1C3 axis significantly impacted NPCs. These findings suggest targeting its downstream pathway may provide new therapeutic approaches IVDD.

Язык: Английский

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Targeting Ferroptosis in Bone-Related Diseases: Facts and Perspectives

Journal of Inflammation Research, Год журнала: 2023, Номер Volume 16, С. 4661 - 4677

Опубликована: Окт. 1, 2023

Abstract: Ferroptosis is a new cell fate decision discovered in recent years. Unlike apoptosis, autophagy or pyroptosis, ferroptosis characterized by iron-dependent lipid peroxidation and mitochondrial morphological changes. involved variety of physiological pathological processes. Since its discovery, has been increasingly studied concerning bone-related diseases. In this review, we focus on the latest research progress prospects, summarize regulatory mechanisms ferroptosis, discuss role pathogenesis diseases, such as osteoporosis (OP), osteoarthritis (OA), rheumatoid arthritis (RA), osteosarcoma (OS), well therapeutic potential. Keywords: death, iron accumulation, peroxidation, diseases

Язык: Английский

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Iron metabolism and ferroptosis in diabetic bone loss: from mechanism to therapy

Frontiers in Nutrition, Год журнала: 2023, Номер 10

Опубликована: Май 5, 2023

Osteoporosis, one of the most serious and common complications diabetes, has affected quality life a large number people in recent years. Although there are many studies on mechanism diabetic osteoporosis, information is still limited no consensus. Recently, researchers have proven that osteoporosis induced by diabetes mellitus may be connected to an abnormal iron metabolism ferroptosis inside cells under high glucose situations. However, comprehensive reviews reported. Understanding these mechanisms important implications for development treatment osteoporosis. Therefore, this review elaborates changes bones conditions, consequences elevated microenvironment associated cells, impact conditions signaling pathways contribute bone loss presence metabolism. Lastly, we also elucidate discuss therapeutic targets with relevant medications which provides some inspiration its cure.

Язык: Английский

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Global research landscape on the crosstalk between ferroptosis and musculoskeletal diseases: A bibliometric and visualized analysis

Heliyon, Год журнала: 2023, Номер 9(12), С. e23113 - e23113

Опубликована: Дек. 1, 2023

Over the past 11 years, mounting evidence has suggested a significant association between ferroptosis and development progression of musculoskeletal (MSK) diseases, such as osteoporosis osteoarthritis. However, comprehensive bibliometric analysis summarizing relationship MSK diseases is currently lacking. The present study collected articles reviews on topic in diseases. data were from January 1st, 2012 to June 30th, 2023 by screening Web Science database. Various tools, including VOSviewer, CiteSpace, Pajek, R package, others, used conduct visualization analyses. Notably, China, USA, Italy emerged primary contributors, jointly accounting for over 80 % published documents, thereby shaping research this domain. Among diverse institutions, Shanghai Jiao Tong University, Soochow Huazhong University Technology displayed highest productivity levels. most prolific authors include Sun Kai, Shang Peng, Jing Xingzhi. Oxidative Medicine Cellular Longevity stood out with largest number publications area. five disorders field are bone fractures, osteosarcoma, neoplasms, joint osteoporotic fractures. This represents an inaugural analysis, presenting holistic view knowledge framework developmental patterns concerning previous eleven years. information can aid researchers acquiring thorough grasp domain offer invaluable insights forthcoming explorations.

Язык: Английский

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Exploration and breakthrough in the mode of chondrocyte death - A potential new mechanism for osteoarthritis

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 115990 - 115990

Опубликована: Дек. 6, 2023

Osteoarthritis (OA) is a frequent chronic joint disease in orthopedics that effects individuals and society significantly. Obesity, aging, genetic susceptibility, misalignment are all known risk factors for OA, but its pathomechanism still poorly understood. Researches have revealed OA much complex process related to inflammation, metabolic chondrocyte death. It can affect parts of the characterized by causing death extracellular matrix descent. Previously, was thought develop from excessive mechanical loading leading destruction articular cartilage. Since some programmed cell deaths share pattern destruction, it likely also involves Even though apoptosis pyroptosis been investigated clarifing solely conventional pathways insufficient understand pathophysiology osteoarthritis. With more researches, has discovered osteoarthritis other new processes, including PANoptosis, ferroptosis, senescence, strongly associated. Among these, PANoptosis combines key traits pyroptosis, apoptosis, necrotic into highly coordinated dynamically balanced inflammatory mechanism. Furthermore, we think PANopotosis might obstruct necroptosis senescence. Therefore, order offer direction therapeutic treatment, evaluate development research on multiple chondrocytes OA.

Язык: Английский

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Current insights into the functional roles of ferroptosis in musculoskeletal diseases and therapeutic implications

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Фев. 3, 2023

Ferroptosis is a novel type of cell death associated with iron accumulation and excessive lipid peroxidation. Elucidating the underlying molecular mechanisms ferroptosis intensively related to development treatment multiple diseases, including musculoskeletal disorders. Moreover, in vitro vivo studies have shown importance oxidative stress conditions such as osteoporosis, osteoarthritis, rheumatoid arthritis, osteosarcoma. Ferroptosis-derived clinical management diseases offers tremendous attractive opportunities. Notably, agonists been proven enhance sensitivity osteosarcoma cells conventional therapeutic strategies. In this review, we mainly focused on implications regulation pathophysiology response Understanding roles for controlling might provide directions ferroptosis-driven therapies, which could be promising

Язык: Английский

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Botulinum toxin A attenuates osteoarthritis development via inhibiting chondrocyte ferroptosis through SLC7Al1/GPX4 axis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1870(5), С. 167215 - 167215

Опубликована: Май 6, 2024

Язык: Английский

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