FAM96B negatively regulates FOSL1 to modulate the osteogenic differentiation and regeneration of periodontal ligament stem cells via ferroptosis DOI Creative Commons
Qianyi Qin, Haoqing Yang, Runzhi Guo

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 18, 2024

Periodontal ligament stem cell (PDLSC)-based therapy is one of the methods to assist bone regeneration. Understanding functional regulation PDLSCs and mechanisms involved a crucial issue in This study aimed explore roles family with sequence similarity 96 member B (FAM96B) PDLSCs. To assess osteogenic differentiation PDLSCs, alkaline phosphatase (ALP) activity assay, Alizarin red staining, quantitative calcium analysis, marker detection were conducted. Transplantation under dorsum nude mice into rat calvarial defects also performed. Then, FAM96B-overexpressed used for RNA-sequencing bioinformatic analysis. evaluate ferroptosis cytosolic reactive oxygen species (ROS), expression glutathione peroxidase 4 (GPX4), mitochondrial morphology functions including ROS, mitochondria membrane potential, respiration detected. The indicators ALP activity, level mineralization, osteocalcin decreased by FAM96B, which demonstrated that FAM96B inhibited knockdown promoted new formation subcutaneously transplanted mice. related biological detected was focused. enhanced ROS GPX4 Hence, Meanwhile, we found inhibition upregulated target gene FOS like 1, AP-1 transcription factor subunit (FOSL1) FOSL1 vitro. defects. inhibitory effect on confirmed. depletion suppressed negatively regulated downstream via ferroptosis. our findings provided foundation understanding FAM96B-FOSL1 axis acting as MSC mediated

Language: Английский

BMP4-GPX4 can improve the ferroptosis phenotype of retinal ganglion cells and enhance their differentiation ability after retinal stem cell transplantation in glaucoma with high intraocular pressure DOI Creative Commons

Chuankai Fang,

Di He,

Yafen Qian

et al.

Human Molecular Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Abstract Activation of bone morphogenetic protein (BMP) 4 signaling promotes the survival retinal ganglion cell (RGC) after acute injury. In this study, we investigated role BMP4 pathway in regulating degeneration cells (RGCs) a mouse glaucoma model and its potential application stem cell. Our results demonstrate that BMP4-GPX4 not only reduces oxidative stress iron accumulation but also neuroprotective factors support transplanted RSCs into host retina. These findings suggest novel therapeutic approach for involving modulation to protect RGCs improve visual function through enhanced RSC differentiation.

Language: Английский

Citations

0
Amarogentin suppresses cell proliferation and EMT process through inducing ferroptosis in colorectal cancer DOI Creative Commons
Chao Wang,

Zhou You,

Guoqing Zhou

et al.

BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 30, 2025

Colorectal cancer (CRC) is one common tumor with the high death rate, and badly affects normal lives of CRC patients. Amarogentin (AG) has been found to exhibit regulatory roles join into progression multiple diseases. However, impacts associated molecular mechanisms AG in keep unclear. In this study, it was demonstrated that weakened cell viability a concentration- time-dependent manner. addition, accelerated apoptosis by triggering ferroptosis. The invasion EMT process were restrained after treatment, but these reversed Fer-1 addition. Moreover, uncovered retarded Nrf2/HO-1/GPX4 activation. Additionally, modulated PTC stimulated At last, illustrated suppressed growth vivo. conclusion, disclosed proliferation through inducing ferroptosis CRC, This discovery suggested may be effective drug for ameliorating progression.

Language: Английский

Citations

0
Targeting ferroptosis: opportunities and challenges of mesenchymal stem cell therapy for type 1 diabetes mellitus DOI Creative Commons
Le Dai, Qing Wang

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 4, 2025

Abstract Type 1 diabetes mellitus (T1DM) is characterized by progressive β-cell death, leading to loss and insufficient insulin secretion. Mesenchymal stem cells (MSCs) transplantation currently one of the most promising methods for replacement therapy. However, recent studies have shown that ferroptosis not only key mechanisms but also reasons extensive cell death within a short period time after MSCs transplantation. Ferroptosis new type regulated (RCD) iron-dependent accumulation lipid peroxides. Due weak antioxidant capacity β-cells, they are susceptible cytotoxic stimuli such as oxidative stress (OS), therefore ferroptosis. Transplanted extremely perturbations in their microenvironment, especially OS, which can weaken induce through In pathophysiological process T1DM, large amount reactive oxygen species (ROS) produced, causing OS. Therefore, targeting may be way protect β-cells improve therapeutic effect This review reviews research related MSCs, summarizes developed strategies help inhibit study aims understand mechanism transplantation, emphasize importance protecting improving survival function transplanted provide direction therapy T1DM future.

Language: Английский

Citations

0
Osteosarcoma Cells and Undifferentiated Human Mesenchymal Stromal Cells Are More Susceptible to Ferroptosis than Differentiated Human Mesenchymal Stromal Cells DOI Creative Commons
Yuliya Smirnova, Dominik Hanetseder,

Lukas Derigo

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 189 - 189

Published: Feb. 6, 2025

Current research suggests that promoting ferroptosis, a non-apoptotic form of cell death, may be an effective therapy for osteosarcoma, while its inhibition could facilitate bone regeneration and prevent osteoporosis. Our objective was to investigate whether the susceptibility regulation ferroptosis differ between undifferentiated (UBC) differentiated (DBC) human marrow stromal cells, as well osteosarcoma cells (MG63). Ferroptosis induced by either inhibiting glutathione peroxidase 4 (GPX4) using RSL3 or blocking all glutathione-dependent enzymes through glutamate/cysteine antiporter with Erastin. Lipid peroxidation assessed fluorescent probe BODIPY™581/591C11, Ferrostatin-1 used inhibit ferroptosis. We demonstrate neither Erastin nor induces in DBC. However, both induce UBC, predominantly MG63 cells. data suggest induction hBMSCs is primarily regulated GPX4, whereas S-Transferase P1 (GSTP1) plays key role controlling In conclusion, targeting pathways involved across different types improve efficacy cancer treatments minimizing collateral damage supporting regenerative processes, minimal impact on therapy.

Language: Английский

Citations

0
Genistein-Loaded, Quaternized Dextran/ Κ-Carrageenan Gels for Bone Regeneration in Osteoporotic Conditions DOI

Deepa Negi,

Manisha Bharti, Yashveer Singh

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
4-Octyl Itaconate Attenuates Postmenopausal Osteoporosis by Inhibiting Ferroptosis and Enhancing Osteogenesis via the Nrf2 Pathway DOI Creative Commons
You Li, Li Yang, Pengfei Li

et al.

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Bone marrow mesenchymal stem cells (BMSCs) play an important role in bone metabolism and tissue repair, their ability to differentiate into osteoblasts is crucial the treatment of diseases such as postmenopausal osteoporosis (PMOP). However, function BMSCs may be affected by ferroptosis. Ferroptosis a cell death mode characterized excess Fe2+ lipid peroxidation, which significantly affects survival rate differentiation BMSCs. This study investigated effect exogenous itaconate derivative 4-octyl (4-OI) on Erastin-induced The results showed that 4-OI inhibited ferroptosis activating nuclear factor erythroid 2-related 2 (Nrf2) signaling pathway, reduced reactive oxygen species levels oxidative damage, restored antioxidant capacity. At same time, promoted osteogenic Further experiments Nrf2-IN-1, inhibitor Nrf2 could reverse protective 4-OI. In vivo, was shown reduce loss ovariectomized (OVX) mice, assessed Micro-CT analysis. Immunofluorescence staining further revealed increased GPX4 expression vertebral tissues following treatment. These indicate improves enhances providing new research ideas potential targets for PMOP.

Language: Английский

Citations

0
Porphyran Inhibits Osteoclast Formation Based on Nf-Κb Signaling Pathway and Accelerates Alveolar Bone Healing in Ovariectomized Mice DOI
Pei Wu, Yizhou Wang, Zehua Duan

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Melatonin attenuates spinal cord injury by regulating ferroptosis through the Nrf2/HO-1/GPX4 pathway DOI Creative Commons

Zhengxi Yu,

Dingwei Wu, Tengbin Shi

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Abstract Spinal cord injury (SCI) is one of the most devastating and catastrophic types injury, with high rates mortality disability. Ferroptosis has become target many major incurable human diseases. By inhibiting ferroptosis, melatonin (MT) can reduce damage in various organs, but protective effect MT on SCI not been reported yet. The modified Ellen's method was used to establish an rat model. spinal neurons recovery motor function were observed. In vitro experiments, oxygen-glucose deprivation/reoxygenation (OGD/R) model established by using mouse hippocampal neuron (HT22) cells simulate ischemia-reperfusion injury. A ferroptosis directly induced Erastin also used. nuclear factor erythroid 2-related 2 (Nrf2) inhibitor ML 385 further detect mechanism through which inhibits protects neuronal cells. Our study demonstrates that rats, promote behavior injured tissue after SCI. Under electron microscope, inhibited rescued damaged mitochondria, partially restored mitochondrial structure. ML385, Nrf2 inhibitor, reversed effects MT. Overall, may alleviate early activating Nrf2/heme oxygenase-1(HO-1)/glutathione peroxidase 4 (GPX 4) pathway.

Language: Английский

Citations

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Decoding ferroptosis: transforming orthopedic disease management DOI Creative Commons

Guochen Huo,

Yumeng Lin,

Lusheng Liu

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 6, 2024

As a mechanism of cell death, ferroptosis has gained popularity since 2012. The process is distinguished by iron toxicity and phospholipid accumulation, in contrast to autophagy, apoptosis, other death mechanisms. It implicated the advancement multiple diseases across body. Researchers currently know that osteosarcoma, osteoporosis, orthopedic disorders are caused NRF2, GPX4, star proteins. effective relief osteoarthritis symptoms from deterioration been confirmed clinical treatment with inhibitors. At same time, it should be reminded mechanisms involved regulate not understood. In this manuscript, we present discovery ferroptosis, role variety diseases. We expect manuscript can provide new perspective on diagnosis related

Language: Английский

Citations

1
Natural Products in the Prevention of Degenerative Bone and Joint Diseases: Mechanisms Based on the Regulation of Ferroptosis DOI Open Access

Kuanhui Gao,

Lizhi Lv, Zhichao Li

et al.

Phytotherapy Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Degenerative bone and joint diseases (DBJDs), characterized by osteoporosis, osteoarthritis, chronic inflammation of surrounding soft tissues, are systemic conditions primarily affecting the skeletal system. Ferroptosis, a programmed cell death pathway distinct from apoptosis, autophagy, necroptosis. Accumulating evidence suggests that ferroptosis is intricately linked to pathogenesis DBJDs, targeting its regulation could be beneficial in managing these conditions. Natural products, known for their anti-inflammatory antioxidant properties, have shown unique advantages preventing potentially through modulating ferroptosis. This article provides an overview latest research on ferroptosis, with focus role DBJDs therapeutic potential natural products this pathway, offering novel insights prevention treatment DBJDs.

Language: Английский

Citations

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