Ferroptosis in Osteocytes as a Target for Protection Against Postmenopausal Osteoporosis

Advanced Science, Journal Year: 2024, Volume and Issue: 11(12)

Published: Jan. 17, 2024

Abstract Ferroptosis is a necrotic form of iron‐dependent regulatory cell death. Estrogen withdrawal can interfere with iron metabolism, which responsible for the pathogenesis postmenopausal osteoporosis (PMOP). Here, it demonstrated that estrogen induces accumulation in skeleton and ferroptosis osteocytes, leading to reduced bone mineral density. Furthermore, facilitatory effect osteocytes verified occurrence development associated over activated osteoclastogenesis using direct osteocyte/osteoclast coculture system glutathione peroxidase 4 (GPX4) knockout ovariectomized mice. In addition, nuclear factor erythroid derived 2‐related factor‐2 (Nrf2) signaling pathway confirmed be crucial osteocytic cells. Nrf2 regulates expression kappa‐B ligand (RANKL) by regulating DNA methylation level RANKL promoter mediated methyltransferase 3a (Dnmt3a), as an important mechanism ferroptosis‐mediated osteoclastogenesis. Taken together, this data suggests involved PMOP targeted tune homeostasis.

Language: Английский

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Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis

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

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Mechanisms of Ferroptosis in bone disease: A new target for osteoporosis treatment

Cellular Signalling, Journal Year: 2025, Volume and Issue: 127, P. 111598 - 111598

Published: Jan. 7, 2025

Language: Английский

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Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(6)

Published: May 18, 2023

Abstract The relationship of obesity and osteoporosis has been widely studied over the past years. However, implications for bone health remain controversial, underlying molecular mechanism is not yet fully understood. This study demonstrated that high‐fat diet‐induced leads to significantly decreased volume/tissue volume (BV/TV), trabecular number (Tb.N), cortical thickness (Ct.Th) male rat femur after mechanical loading effects body weight were controlled. HFD‐induced obese rats exhibited attenuated expression ferroptosis inhibitory protein SLC7A11 GPX4 in tissues, which was correlated with elevated serum TNF‐α concentration. Ferroptosis inhibitor administration could effectively rescue osteogenesis‐associated type H vessels osteoprogenitors, downregulate levels ameliorate loss rats. Since both affect vessel formation, we further investigated interaction between TNF‐α, its impact osteogenesis angiogenesis vitro. In human osteoblast‐like MG63 umbilical vein endothelial cells (HUVEC), TNF‐α/TNFR2 signaling promoted cystine uptake GSH biosynthesis provide protection against low‐dose inducer erastin. While, TNF‐α/TNFR1 facilitated presence high‐dose erastin through ROS accumulation. Moreover, regulated ferroptosis‐induced osteogenic angiogenic dysfunctions based on regulatory role. Meanwhile, inhibitors reduce intracellular overproduction enhance TNF‐α‐treated HUVECs. revealed angiogenesis, provides new insights into pathogenesis regenerative therapy obesity‐related osteoporosis.

Language: Английский

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The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings

Biomolecules, Journal Year: 2023, Volume and Issue: 13(6), P. 1006 - 1006

Published: June 17, 2023

The objective of the present study was to review recent epidemiological and clinical data on association between selected minerals trace elements osteoporosis, as well discuss molecular mechanisms underlying these associations. We have performed a search in PubMed-Medline Google Scholar databases using MeSH terms "osteoporosis", "osteogenesis", "osteoblast", "osteoclast", "osteocyte" with names particular through 21 March 2023. demonstrate that physiological nutritional levels promote osteogenic differentiation up-regulation BMP-2 Wnt/β-catenin signaling, other pathways. miRNA epigenetic effects were also involved regulation minerals. antiresorptive effect associated inhibition osteoclastogenesis. At same time, bone health appeared be dose-dependent low doses promoting an effect, whereas high exerted opposite which promoted resorption impaired formation. Concomitant results laboratory studies, several trials studies demonstrated supplementation Zn, Mg, F, Sr may improve quality, thus inducing antiosteoporotic effects.

Language: Английский

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Picein alleviates oxidative stress and promotes bone regeneration in osteoporotic bone defect by inhibiting ferroptosis via Nrf2/HO‐1/GPX4 pathway

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(7), P. 4066 - 4085

Published: May 10, 2024

Abstract Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to abnormal oxidative stress and high levels of reactive oxygen species (ROS), a detrimental for formation, making OP‐related healing significant clinical challenge. As osteogenic differentiation ability marrow mesenchymal stem cells (BMSCs) is closely related regeneration; currently, this study assessed effects Picein on BMSCs vitro osteoporotic defect vivo. Cell viability was determined by CCK‐8 assay. The production malonaldehyde, superoxide dismutase activities, glutathione evaluated using commercially available kits, flow cytometry analysis adopted detect macrophage polarization. Osteogenic capacity alkaline phosphatase (ALP) activity, ALP staining, Alizarin red S staining. expression osteogenic‐related proteins (OPN, Runx‐2, OCN) genes (ALP, BMP‐4, COL‐1, Osterix) were Western blotting real‐time PCR (RT‐PCR). In addition, proliferation, migration ability, angiogenic human umbilical vein endothelial (HUVECs) EdU scratch test, transwell assay, tube formation respectively. Angiogenic‐related (VEGF, vWF, CD31) also RT‐PCR. Results showed that alleviated erastin‐induced stress, enhanced BMSCs, angiogenesis HUVECs, protects against ferroptosis through Nrf2/HO‐1/GPX4 axis. Moreover, regulate immune microenvironment promoting polarization M2 macrophages vitro. reduce inflammation promotes OP rat models Altogether, these results suggested promote alleviate via pathway, offering as novel antioxidant agent treating defect.

Language: Английский

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Eldecalcitol protected osteocytes against ferroptosis of D-gal-induced senescent MLO-Y4 cells and ovariectomized mice

Experimental Gerontology, Journal Year: 2024, Volume and Issue: 189, P. 112408 - 112408

Published: March 23, 2024

Active vitamin D analog eldecalcitol is clinically applied in treatment of postmenopausal osteoporosis. This study aims to determine the role protection osteocytes from senescence and associated ferroptosis. The MLO-Y4 were exposed D-gal inducing senescence. ovariectomized (OVX) mice treated with using as an aging inducer intraperitoneally injected eldecalcitol. multiplexed confocal imaging, fluorescence situ hybridization transmission electron microscopy assessing osteocytic properties. Immunochemical staining immunoblotting carried out detect abundance expression molecules. ablation receptor led a reduction amounts osteocytes, loss dendrites, increase mRNA SASP factors protein senescent factors, well changes ferroptosis-related genes (PTGS2 & RGS4). Eldecalcitol reversed phenotypes cells shown by improving cell morphology density, decreasing β-gal-positive accumulation, down-regulating (P16, P21 P53). reduced intracellular ROS MDA productions, elevated JC-1 aggregates, up-regulated Nrf2 GPX4. exhibited osteopreserve effects D-gal-induced OVX mice. imaging displayed its improvement on network organization. decreased numbers at tibial diaphysis SADS assay attenuated down-regulated senescence-related restored levels ferroptotic biomarkers osteocytes-enriched bone fraction. It 4-HNE area, stimulated Nrf2-positive staining, promoted nuclear translocation inhibited Nrf2, respectively, present revealed ameliorative ferroptosis contributing preservation against osteoporosis

Language: Английский

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Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: 180, P. 82 - 103

Published: April 15, 2024

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels reactive oxygen species (ROS), condition detrimental for formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative functions prevent loss facilitate regeneration in OP. In the current study strategy one-pot method by introducing Poly (lactic acid-carbonate) (PDT) β-Tricalcium Phosphate (β-TCP) SeNPs, developed prepare an injectable, anti-collapse, shape-adaptive adhesive graft substitute material (PDT-TCP-SE). PDT-TCP-SE exhibits sufficient adhesion biological microenvironments osteoinductive activity, angiogenic anti-inflammatory well vitro vivo. Moreover, protect BMSCs from erastin-induced ferroptosis through Sirt1/Nrf2/GPX4 antioxidant pathway, which, together, demonstrated emerging biomaterial potential application future defects. Injectable, adhesive, plastic bioactive was successfully synthesized. Incorporation SeNPs PDT into β-TCP regenerated new in-situ moderating defects area. reduced ROS microenvironment. could also moderate inhibit via pathway vitro. alleviate inflammatory environment promote This has advantages simple synthesis, biocompatibility, regulation level, value tissue engineering.

Language: Английский

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CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

Aging, Journal Year: 2024, Volume and Issue: 16(10), P. 8965 - 8979

Published: May 22, 2024

Bone formation and homeostasis are greatly dependent on the osteogenic differentiation of human bone marrow stem cells (BMSCs). Therefore, revealing mechanisms underlying BMSCs will provide new candidate therapeutic targets for osteoporosis.

Language: Английский

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Aucubin Promotes BMSCs Proliferation and Differentiation of Postmenopausal Osteoporosis Patients by Regulating Ferroptosis and BMP2 Signalling

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)

Published: Jan. 1, 2025

Postmenopausal osteoporosis (PMOP) is a chronic systemic bone metabolism disorder. Promotion in the patterns of human marrow mesenchymal stem cells (hBMSCs) differentiation towards osteoblasts contributes to alleviating osteoporosis. Aucubin, natural compound isolated from well-known herbal medicine Eucommia, was previously shown possess various pharmacological effects. However, its effects on hBMSCs PMOP patients are unknown. The aim this present research investigate impact and underlying process aucubin cell proliferation osteogenic patients. ability inhibit ferroptosis induced by erastin detected; ROS production, ferrous ion levels, SOD, MDA, GPX activities were tested using commercial kits. Next, ALP staining, ARS RT-qPCR, RNA-sequencing, Western blot applied for determining mRNA protein expression levels associated with osteogenesis hBMSCs. study also explored involvement BMP2/Smads signalling promoting evaluated intervention an ovariectomised rat model. results indicated that significantly inhibited generation oxidative stress protected against Additionally, facilitated activating BMP2/SMADs pathway attenuated progression OVX rats, suggesting potential therapeutic benefit postmenopausal (PMOP).

Language: Английский

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