Targeting oxidative stress, iron overload and ferroptosis in bone-degenerative conditions DOI Creative Commons
Junxiao Ren, Chen Meng, Li Rui

et al.

Turkish Journal of Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Abstract Introduction Bone-degenerative conditions, including osteoporosis, rheumatoid arthritis, and osteoarthritis, are major public health concerns worldwide, associated with oxidative stress iron overload that disrupts bone homeostasis. Ferroptosis, an iron-mediated form of cell death, has emerged as a critical factor in degeneration, necessitating comprehensive review its role these conditions. Content This comprehensively examined the latest research on stress, metabolism, ferroptosis related to biology focusing their interconnections potential therapeutic implications. The revealed affects various types, osteoclasts, osteoblasts, chondrocytes, contributing loss cartilage degradation. Iron homeostasis was found be crucial for function, both deficiency potentially leading pathological Ferroptosis regulation involves complex interplay between lipid peroxidation, antioxidant systems, SLC7A11-GSH-GPX4 network FSP1-CoQ10H2 pathway. Different lineages, mesenchymal stem cells, exhibit varied responses induction regulation. Summary Understanding molecular mechanisms underlying cells offers promising avenues developing targeted therapies bone-degenerative Outlook Future should focus elucidating specific roles different disorders exploring interventions targeting overload, pathways improve management debilitating

Language: Английский

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis DOI Creative Commons
Yili Chen, Wen Zhao,

An Bin Hu

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 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

Language: Английский

Citations

19
An Osteoimmunomodulatory Biopatch Potentiates Stem Cell Therapies for Bone Regeneration by Simultaneously Regulating IL‐17/Ferroptosis Signaling Pathways DOI Creative Commons
Shan Liu, Wenle Wang, Zhiyu Chen

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

Currently, there are still great challenges in promoting bone defect healing, a common health problem affecting millions of people. Herein an osteoimmunity-regulating biopatch capable stem cell-based therapies for regeneration is developed. A totally biodegradable conjugate first synthesized, which can self-assemble into bioactive nano micelles (PPT NMs). This nanotherapy effectively improves the osteogenesis periodontal ligament cells (PDLSCs) under pathological conditions, by simultaneously regulating IL-17 signaling and ferroptosis pathways. Incorporation PPT NMs electrospun nanofibers affords patch, notably formation two rat models. Janus bio patch then engineered integrating with cell sheet PDLSCs. The obtained shows additionally potentiated capacity, synergistically osteoimmune microenvironment facilitating differentiation. Further surface functionalization tannic acid considerably increases its adhesion to defect, prolongs local retention, sustains bioactivities, thereby offering much better repair effects rats mandibular or cranial defects. Moreover, patches display good safety. Besides defects, this strategy be applied promote spinal cord injury, wound skin burns.

Language: Английский

Citations

10
Association of dietary carbohydrate intake with bone mineral density, osteoporosis and fractures among adults without diabetes: Evidence from National Health and Nutrition Examination Survey DOI Creative Commons
Ran Chen,

Kai Gong,

Wei Chen

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(15), P. e35566 - e35566

Published: Aug. 1, 2024

Language: Английский

Citations

4
Silencing of LOX-1 attenuates high glucose-induced ferroptosis in THVECs via the HIF-1α/SLC7A11 signaling pathway DOI

Haiqi Zhang,

Xinying Chang,

X. Liu

et al.

Experimental Cell Research, Journal Year: 2025, Volume and Issue: 446(2), P. 114451 - 114451

Published: Feb. 25, 2025

Language: Английский

Citations

0
SUGAR-seq reveals the transcriptome and N-linked glycosylation landscape of mononuclear phagocytes at single-cell resolution in a mouse model of autosomal dominant osteopetrosis type 2 DOI Creative Commons
Yu Sha, Lingyu Huang, Lei Zhang

et al.

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 31, 2025

Heterozygous mutation of CLCN7 (R286W) is commonly found in patients with benign autosomal dominant osteopetrosis. However, there no evidence from animal models to confirm that it a disease mutation. And the characteristics bone marrow cell (BMC) landscape osteopetrosis at single-cell level are completely unknown till now. In this study, we generated first type 2 (ADO2) mouse model typical phenotypes carried Clcn7 (r284w) corresponding observed human using gene editing technology. then, conducted first-ever analysis RNA expression and N-linked glycosylation profiles for BMCs by SUrface-protein Glycan RNA-sequencing (SUGAR-seq). We identified 14 distinct types similar proportion neutrophils both ADO2 wild mice, confirmed flow cytometry analysis. The modifications were significantly downregulated detecting SUGAR-seq, which was situation N-Glycan profiling 4D Label-Free N-Glycosylation Proteomics Analysis. Particularly noteworthy heterogeneity classic monocytes. six subtypes, but only two subtypes different cell, whose expressed genes associated NF-κB-inducing kinase / Nuclear Factor-kappa B (NIK/NF-κB) signaling other pathway osteoclast differentiation. Our murine confirms pathogenic ADO2. Additionally, our analyses reveal monocytes ADO2, abnormal across various may represent important events pathogenesis

Language: Английский

Citations

0
The Role of Ferroptosis in Osteoporosis and Advances in Chinese Herbal Interventions DOI Creative Commons
Pan Li, Tianyang Xu,

Ao-xue Yu

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(4), P. 367 - 367

Published: April 2, 2025

OP, a systemic bone disorder marked by reduced mass and heightened fracture risk, poses significant global health burden, particularly among aging populations. Current treatments, including bisphosphonates calcium supplementation, are limited adverse effects incomplete efficacy. Emerging research highlights ferroptosis—an iron-dependent cell death driven lipid peroxidation—as critical contributor to OP pathogenesis, characterized dysregulated iron metabolism, oxidative stress, peroxide accumulation, which disrupt remodeling impairing osteoblast function enhancing osteoclast activity. This review elucidates the mechanistic interplay between ferroptosis subtypes (diabetic osteoporosis (DOP), glucocorticoid-induced (GIOP), postmenopausal (PMOP)) evaluates efficacy of Chinese herbal interventions in mitigating ferroptosis-driven loss. Key findings reveal that excess exacerbates peroxidation via Fenton reaction, while glutathione peroxidase 4 (GPX4) inactivation system Xc- inhibition amplify damage. In DIOP, hyperglycemia-induced ROS advanced glycation end products suppress osteogenesis, countered melatonin naringenin nuclear factor -related 2 (Nrf2)/GPX4 activation. GIOP involves dexamethasone-mediated GPX4 downregulation, mitigated exosomes through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target rapamycin (mTOR) signaling. PMOP estrogen deficiency-induced overload is alleviated aconitine icariin (ICA) kappa-light-chain-enhancer activated cells (NF-κB) signal transducer activator transcription 3 (STAT3) pathways. herbs, active compounds (quercetin, gastrodin, ICA, etc.) formulations (Bugu Shengsui Capsule, Erxian Decoction (EXD), etc.), regulate enhance antioxidant defenses (Nrf2/heme oxygenase 1(HO-1)), inhibit peroxidation, effectively restoring homeostasis. These underscore as pivotal mechanism progression highlight therapeutic promise herbs bridging traditional medicine with modern insights. Future should prioritize elucidating precise molecular targets, optimizing formulations, validating clinical address current gaps.

Language: Английский

Citations

0
Qing'e Pill Rectifies Bone Homeostasis Imbalance in Diabetic Osteoporosis via the AGE/RAGE Pathway: A network pharmacology analysis and multi-omics validation DOI
Yingjie Wang, Yang Yao, Yuan Chen

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119816 - 119816

Published: April 1, 2025

Language: Английский

Citations

0
Different Forms of Regulated Cell Death in Type-2-Diabetes-Mellitus-Related Osteoporosis: A Focus on Mechanisms and Therapeutic Strategies DOI Open Access

Chenchen Li,

He Gong,

Peipei Shi

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4417 - 4417

Published: May 6, 2025

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with high prevalence and challenging treatment options. It significantly affects the function of various organs, including bones, imposes substantial social economic costs. Chronic hyperglycemia, insulin resistance, abnormalities in glucolipid metabolism can lead to cellular damage within body. Bone dysfunction represents significant characteristic diabetic osteoporosis (DOP). Recent studies confirm that cell death critical factor contributing bone damage. Regulated (RCD) highly controlled process involves numerous proteins specific signaling cascades. RCD processes, apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, cuproptosis, may be linked cells T2DM. In this review, types populations during pathogenic DOP were explored, link between processes pathogenesis was further explored. addition, research progress on targeting for summarized paper. This provide foundation additional explorations drug development, as well new therapeutic concepts clinical management DOP.

Language: Английский

Citations

0
ATP-induced cell death: a novel hypothesis for osteoporosis DOI Creative Commons
Wei Wang,

Haolong Zhang,

Doblin Sandai

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Dec. 14, 2023

ATP-induced cell death has emerged as a captivating realm of inquiry with profound ramifications in the context osteoporosis. This study unveils paradigm-shifting hypothesis that illuminates prospective involvement cellular demise etiology Initially, we explicate morphological attributes and delve into intricacies molecular machinery regulatory networks governing ATP homeostasis death. Subsequently, our focus pivots towards multifaceted interplay between pivotal protagonists, such bone marrow-derived mesenchymal stem cells, osteoblasts, osteoclasts, accentuating their potential contributions to secondary osteoporosis phenotypes, encompassing diabetic osteoporosis, glucocorticoid-induced postmenopausal Furthermore, probe alternative modalities demise, apoptosis, autophagy, necroptosis. Through an all-encompassing intricate nexus connecting primary goal is deepen comprehension underlying mechanisms propelling this malady establish theoretical bedrock underpin development pioneering therapeutic strategies.

Language: Английский

Citations

9
Flavonoids attenuate inflammation of HGF and HBMSC while modulating the osteogenic differentiation based on microfluidic chip DOI Creative Commons

Sa Du,

Zhongyu Wang, Huilin Zhu

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 2, 2024

When inflammation occurs in periodontal tissues, a dynamic cellular crosstalk interacts between gingival fibroblasts and bone marrow mesenchymal stem cells (BMSCs), which plays crucial role the biological behaviour differentiation of cells. Recently, flavonoids are increasingly recognized for their therapeutic potential modulating osteogenic differentiation. Owing to varied molecular structures mechanisms, there more needs that flavonoid compounds should be identified by extensive screening. However, current drug research mostly relies on static, single-type cell cultures. In this study, an innovative bionic microfluidic chip system tailored both soft hard tissues was developed screen suitable treating periodontitis.

Language: Английский

Citations

3